Mineralocorticoids and Aldosterone Flashcards

1
Q

What are the three layers of the adrenal cortex?

A

Zona glomerulosa
Zona fasciculata
Zona reticularis

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2
Q

What does the zona glomerulosa do?

A

Produces mineralocorticoids (aldosterone)

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3
Q

What does the zona fasciculata do?

A

Produces glucocorticoids (cortisol) and androgens

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4
Q

What does the zona reticularis do?

A

Produces androgens

Specialized to secrete Dihydroepiandrosterone

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5
Q

What does the adrenal medulla do?

A

Epinephrine

Small amount of norepinephrine

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6
Q

Largest region of the cortex?

A

Zona fasciculata

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7
Q

Key enzyme in the zona glomerulosa needed for mineralocorticoids?

A

21-hydroxylase enzyme

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8
Q

Key enzyme in the zona fasciculata needed for cortisol?

A

21-hydroxylase

11-Beta-hydroxylase

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9
Q

What is the common step to formation of all the steroids?

A

StAR needed for cholesterol to produce Pregnenolone

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10
Q

Most common abnormalities to form adrenal gland dysfunction?

A

21-hydroxylase

11-Beta-hydroxylase

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11
Q

What is the first step in steroid synthesis?

A

Get cholesterol into the mitochondria

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12
Q

What transports cholesterol into the mitochondria?

A

StAR protein

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13
Q

What generates Pregnenolone from cholesterol?

A

Cholesterol side-chain cleavage enzyme

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14
Q

GFR mnemonic:

A

G: Salt (mineralocorticoids)
F: Sugar (glucocorticoids)
R: Sex (androgens)

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15
Q

What does ACTH stimulate production of?

A

Both cortisol and adrenal androgens

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16
Q

What is the feedback for ACTH inhibition?

A

Cortisol only

No androgen feedback to inhibit ACTH

17
Q

What receptor does ACTH stimulate?

A

MC2R (melanocortin-2 receptor)

18
Q

What is the primary mediator of aldosterone release?

A

A-II; less so by ACTH and K+ levels

19
Q

Three actions of aldosterone on the kidneys:

A
  1. ) Sodium and therefore passive water reabsorption
  2. ) Potassium absorption by the principal cells of the cortical CT
  3. ) Active secretion of protons via proton ATPases in lumenal membrane of IC of CT
20
Q

Three major pathways regulating the secretion of renin by granular cells at the JGA:

A
  1. ) Renal baroreceptors: decreased perfusion = increased renin
  2. ) Macula densa: decreased Na/Cl ions in DCT = increased renin
  3. ) Sympathetic nervous system: increased activity increased renin release via beta receptors
21
Q

How does A-II cause aldosterone release?

A

A-II binding to AT1 receptor causing IP3 binding to IP3R and release of intracellular Ca2+

22
Q

What is the indirect method by which aldosterone inhibits ACTH release?

A

Systems effects of regulating blood volume and blood pressure leads to inhibition of ACTH release

23
Q

What do principle cells express?

A

11beta-HSD2

24
Q

What does 11beta-HSD2 cause?

A

Breaks down glucocorticoids so that they do not have as high of an affinity to the same receptors as mineralocorticoid receptors

25
Q

What does glycyrrhetinic acid do?

A

Inhibits 11beta-HSD2

26
Q

What is a common glycyrrhetinic acid?

A

Carbenoxolone

27
Q

Half-life of aldosterone:

A

15-20 minutes

28
Q

What is Conn’s syndrome?

A

Primary hyperaldosteronism

29
Q

What causes Conn’s syndrome?

A

Autonomous benign tumors of the adrenal gland hyper-secrete aldosterone

30
Q

What does Conn’s syndrome cause?

A

Hypertension bc H20 and Na+ retention and hypokalemia bc excess K+ secretion and suppressed renin release

31
Q

What is secondary hyperaldosteronism?

A

Renin overproduction

32
Q

What can cause secondary hyperaldosteronism?

A

Decrease in effective arterial blood volume associated with ascites or heart failure leading to continuous stimulation of RAS system

33
Q

What can cause primary hypoaldosteronism?

A

Plasma renin levels elevated due to primary adrenal insufficiency

34
Q

What can cause secondary hypoaldosteronism?

A

Inadequate stimulation of aldosterone secretion despite normal adrenal function

35
Q

How can mineralocorticoids cause kidney damage?

A

Production of ROS either by stimulation of NADPH oxidase or via mitochondria

36
Q

What do ROS activated by mineralocorticoids cause in the kidney?

A

Podocyte damage, inflammation and fibrosis

37
Q

How does aldosterone cause mesangial cell proliferation?

A

Activates P13K-AKT and MAPK causing transactivation of EGFR