Adrenal Glands

Question 1

What are the 3 main stresses an organsim responds to? [3]

Answer 1

Hypotension
Infection
Starvation

Question 2

Adrenal Cortex:

Zona [] - adreno androgens. Eg. [].
Zona [] - glucocorticoid hormones eg. []
Zona [] - minerocorticoid hormones eg. []

Answer 2

Adrenal Cortex

Zona reticulars - adreno androgens. Eg. testosterone
Zona fasciculata - glucocorticoid hormones eg. cortisol
Zona glomerulosa - minerocorticoid hormones eg. aldosterone

Question 3

How is direct communication possible between the adrenal cortex and medulla? [1]

Answer 3

No barrier between the medulla and the zona reticulata - so direct communicaton is possible

Question 4

The medulla contains [] cells.

Answer 4

chromaffin cells

Question 5

Cortex – derived from the embryonic [].
Medulla – derived from the [] neural crest cells.

Answer 5

Cortex – derived from the embryonic mesoderm.
Medulla – derived from the ectodermal neural crest cells.

Question 6

What are the 3 arteries that supply the adrenal glands? [3]

Which arteries do they come from? [3]

Answer 6

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.

Question 7

Label A-D

Answer 7

A: superior adrenal artery
B: inferior phrenic artery
C: middle adrenal artery
D: inferior adrenal artery

Question 8

Hyperplasia of the ZF would cause which disease? [1] Because of an overproduction of what? [1]

Answer 8

Cushings disease: high levels of cortisol

Question 9

Why might you see expansion of ZG in body?

Answer 9

If the Na is low in blood: expansion of the ZG to produce more aldosterone.

Question 10

All pathways in the steroidogenic enzyme pathway start with which molecule? [1]

Answer 10

Cholesterol: The different enzymes of the different zones allow cholesterol to be turned into di#erent hormones.

Question 11

Different enzymes expressed in the cortex zones:

ZG: For aldosterone synthesis? [1]
ZF: For cortisol synthesis? [1]
ZR: for testosterone synthesis? [1]

Answer 11

ZG: For aldosterone synthesis: Aldosterone synthase: P450c 11AS
ZF: For cortisol synthesis: p450c 11B-hydroxylase
ZR: for testosterone synthesis: 17a-hydroxylase

Question 12

What is release of aldosterone stimulated by? [2]

Answer 12

rising K+ [1]
fall in blood volume/BP [1]

Question 13

ZG cells are distinguished by expression of the type I [] receptor , [] synthase, low levels of [], and no expression of [].

Answer 13

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)

Question 14

Explain hyperaldosteromism affects the RAAS system

Answer 14

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.

Question 15

RAAS system is triggered by? [4]

Answer 15

Na loss
haemorrhage
upright posture
decreasing renal blood

Question 16

Aldosterone binds to [] receptor

Answer 16

Aldosterone binds to mineralocorticoid receptor

Question 17

The enzyme families that control conversion of cholesterol to adrenal cortex enzymes are? [2]

Answer 17

cytochrome p450
hydroxy-steroid dehydrogenase (HSD) classes.

Question 18

ZG cells express receptors for [] but the main regulators of secretion of aldoseterone are [] and small increases in the extracellular [] concentration.

Answer 18

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

Question 19

mineralocorticoid receptor is activated by which two substrates? [2]

Why is that important? [1]

Answer 19

mineralocorticoid receptor: activated by cortisol AND aldosterone

So in cells where aldosterone is active, cortisol is deactivated otherwise receptor would be overwhelmed

Question 20

What is the role of 11β-HSD2? [1]

Answer 20

11 β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2): converts active cortisol to inactive cortisone and protects mineralocorticoid receptor (MR)

Question 21

Aldosterone renal effects:

Explain MoA of Aldosterone on Principal cell

Answer 21

• 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.

Question 22

Aldosterone renal effects:

Explain MoA of Aldosterone on Intercalated cell?

Answer 22

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.

Question 23

Aldosterone XS causes which 3 physiological changes? [3]

Answer 23

Hypertension, hypokalaemia and metabolic alkalosis.

Question 24

What is Conn’s syndrome aka? [1]

Caused by? [2]

Answer 24

AKA: Primary aldosteronism

can occur from a unilateral adrenal adenoma, or from hyperplasia of the ZG of both adrenal gland

Question 25

What is Liddle syndrome caused by? [1]

What are the symptoms? [3]

C

Answer 25

Caused by: overexpression of ENaC channels

Symptoms: of hyperaldosteronism - Hypertension, hypokalaemia, metabolic alkalosis

Question 26

Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess? [1]

Why does that create symptoms of hyperaldosternism? [1]

Answer 26

When 11BHSD-2 enzyme is supressed/mutated - cortisol isnt deactivated and will binds to MR.

symptoms of hyperaldosteronism

Question 27

Explain MoA of cortisol being released from hypothalamus to adrenal cortex [3]
What receptor is activated to release cortisol? [1]

Answer 27

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

Question 28

Specifically, how does ACTH binding to Melanocortin-2 receptor (ACTH Receptor) work? [3]

Answer 28

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.

Question 29

Which enzyme is the final step in producing cortisol from cholesterol? [1]

Answer 29

CYP11B1

Question 30

Explain with condition of glucocorticoid remediable aldosteronism

Answer 30

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)

Question 31

What can stimulate HPA axis to produce cortisol? [3]

Answer 31

Inflammation
Stress
Circadian rhythm (highest in morning)

Question 32

What effect does increasing cortisol levels have on HPA axis?

Answer 32

-ve feedback: reduces it