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Endorine > Adrenal Physiology (5/16) > Flashcards

Adrenal Physiology (5/16) Flashcards

1
Q

List the parts of the adrenal gland from outside to in

A
  1. Capsule
  2. Zona glomerulosa
  3. Zona fasciculata
  4. Zona reticularis
  5. Adrenal Medulla
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2
Q

What does the zona glomerulosa make?

A

Aldosterone

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3
Q

What does the zona fasciculata make?

A

Glucocorticoids

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4
Q

What does the zona reticularis make?

A

Androgens

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5
Q

What does the adrenal medulla make?

A

Epinephrine

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6
Q

How are adrenocortical hormones made?

A

Synthesized form cholesterol by cytochrome P450 enzymes in the mitochondria and smooth ER of the adrenal gland

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7
Q

What is the rate limiting step in steroid production?

A

Side chain cleavage of cholesterol to pregnenolone by CYP11A1

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8
Q

Why is the glomerulosa cell the only location where glucocortiocids become mineralocortiocids?

A

Only cells with aldosterone synthetase enzyme

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9
Q

Aldosterone is released in response to…?

A

Increased

  • angiotensin
  • serum potassium
  • ACTH (lesser stimulus)
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10
Q

Cortisol is released in response to…?

A

Increased

  • ACTH
  • Arginine vasopressin (lesser stimulus)
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11
Q

Androgens are released in response to…?

A

Increased ACTH

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12
Q

Norepi and epi are released in response to…?

A

Sympathetic nervous system activation and its synthesis is dependent on high local concentrations of cortisol

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13
Q

What does aldosterone regulate?

A

Binds mineralocortioid receptors to regulate blood volume and salt/water homeostasis

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14
Q

What does cortisol regulate?

A

Binds glucocorticoid receptor to regulate energy balance, CV, metabolic and immune homeostasis

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15
Q

What do androgens regulate?

A

Bind androgen receptor to regulate pubarche

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16
Q

What do norepi and epi regulate?

A

Bind adrenergic receptors to regulate CV effects and bronchial dilation

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17
Q

Renin is released in response to…?

A

Decreased afferent arteriole volume/low renal perfusion ie low blood volume coming into kidney (sensed via juxtaglomerular cells) and decreased distal tubule sodium concentration (sensed via macula densa)

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18
Q

Renin is decreased in response to…?

A

Increased afferent volume/high renal perfusion pressure and increased distal tubule sodium concentration (tubuloglomerular feedback)

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19
Q

What stimulates aldosterone release?

A

K+ and angiotensin II stimulate aldosterone synthetase in the zona glomerulosa. ACTH can also stimulate aldosterone synthetase (to a lesser extent).

Aldosterone regulates extracellular volume and potassium balance.

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20
Q

What makes/releases renin?

A

Juxtaglomerular cells. Renin then converts angiotensinogen to angiotensin I which is converted to angiotensin II by ACE. Angiotensin II then stimulates aldosterone release

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21
Q

Where does aldosterone work and how?

A

In the distal cortical collecting duct principal cells. Binds mineralocortioid receptors which leads to inc transcription of Na/K channels bringing more Na into the blood and more K+ out…water follows Na.

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22
Q

What causes CRH to be released?

A

CRH is released in a circadian rhythm. Also physical stressors like hypoglycemia, hypotension, surgery, fever, injury

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23
Q

What cell types does CRH stimulate?

A

Corticotrophs

24
Q

What stimulates ACTH release?

A

CRH, vasopression, pro-inflammatory cytokines (inflammation)

25
Q

What is the negative feedback in cortisol axis?

A

Cortisol has neg feedback on ACTH and CRH

26
Q

What protein is cleaved to make ACTH?

A

POMC is post-translationally cleaved to become melanocyte stimulating hormones, beta endorphin, beta lipotropin and ACTH

27
Q

What is the ACTH specific receptor?

A

Melanocortin 2 receptor on adrenal tissue. It increases LDL receptors to bring in more cholesterol as a precursor for steroid hormones and activates CYP11A1 enzyme for cholesterol side chain cleavage.

28
Q

How else can ACTH fxn?

A

Can fxn as melanocortin, activating the melanocortin 1 receptor expressed on melanocytes

29
Q

Describe cortisol and ACTH secretion rhythms

A

Diurnal Cortisol Secretion

ACTH and cortisol are pulsatile throughout the day and follow a circadian rhythm

30
Q

When is cortisol highest?

A

6-8 hours after sleeping, begins to decline after awakening

31
Q

When is cortisol lowest?

A

Midnight

32
Q

What are cortisols actions on the liver?

A

Gluconeogenesis, decrease glucose uptake

33
Q

What are cortisols actions on skeletal muscle?

A

Release of AAs

Blocks insulin dep glucose uptake (insulin resistance)

34
Q

What are cortisols actions on inflammatory and immune cells?

A

Potent immunosuppressant and anti-inflammatory effects

  • dec macrophage
  • dec T cell
  • dec mast cell degranulation
35
Q

What are cortisols actions on peripheral adipose tissue?

A

Release of free fatty acids and glycerol

36
Q

What are cortisols actions on the heart?

A

Inc BP via vasoconstriction

Inc adrenergic receptor responsiveness

37
Q

What are cortisols actions on bone?

A

Inc osteoclast activity, dec calcium absorption

38
Q

What are cortisols actions on vascular smooth muscle

A

Vasomotor tone
Responsiveness to vasoconstrictors
–>inc BP

39
Q

What are cortisols actions on the adrenal medulla?

A

Epinephrine synthesis (activates PNMT enzyme)

40
Q

What is the cortisone shunt?

A

The mineralocorticoid receptor has higher affinity for cortisol than aldosterone. Aldosterone sensitive tissues (like the kidney) have 11-beta HSD2 enzyme shunt that makes cortisol, cortisone. In the tissues where you need more cortisol, like the liver, 11-beta HSD1 will make cortisone into cortisol

41
Q

What does licorice do?

A

Prevents inactivation of cortisol by inhibiting 11betaHSD2. Leads to activation of MCR by cortisol and therefore hypertension and hypokalemia (a pseudohyperaldosteronism)

42
Q

What are the adrenal androgens?

A

DHEA, DHEAS, androstenedione

43
Q

When is there a natural inc in production of adrenal androgens?

A

With age

44
Q

What is androstenedione converted to?

A

Testosterone and estrone in peripheral tissues

45
Q

Where does medulla receive input from?

A

Sympathetic nervous system through pregang fibers from thoracic spinal cord

46
Q

What are medulla cells like

A

Nerve gang, but lack synapses from postgang fibers and releases secretions directly into blood

47
Q

What is the RLS in catecholamine synthesis?

A

Tyrosine enters chromaffin cells and is converted by tyrosine hydroxylase to dopa, which is the RLS in catecholamine synthesis

48
Q

How does cortisol promote epinephrine synthesis in medulla?

A

Upregulates PNMT, enzyme that converts norepi to epi

49
Q

What % epi and norpei does medulla secrete?

A

20% norepi, 80% epi

50
Q

What can catecholamines be converted to after norepi and epi?

A

Metanephrines (normetanephrine and metanephrine)

51
Q

What is the short life of metanephrines and catecholamines?

A

Short! So they signal through 2nd messenger systems in teh cell

52
Q

What receptors do catecholamines bind?

A

Adrenergic receptors

53
Q

Alpha1 (fxn, location, 2nd messenger)

A

Fxn: Adrenergic receptor leads to vasoconstriction and inc peripheral resistance

Location: Arterial/venous vasculature

2nd messenger: Inc IP3

54
Q

Alpha 2 (fxn, location, 2nd messenger)

A

Fxn: Inhibits insulin release

Location: arterial/venous vasculature, nerve terminals

2nd messenger: Dec cAMP

55
Q

Beta 1 (fxn, location, 2nd messenger)

A

Fxn: Tachycardia, inc myocardial contractility, inc release of renin

Loc: Heart, juxtaglomerular apparatus

2nd m: inc cAMP

56
Q

Beta 2 (fxn, location, 2nd messenger)

A

Fxn: Vasodilation, bronchodilation

Loc: Heart, skeletal muscle, vasculature, bronchial smooth muscle

2nd m: inc cAMP

57
Q

Look at summary slides

A

Look at summary slides

Endorine (24 decks)

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