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Physiology > Adrenal Physiology > Flashcards

Adrenal Physiology Flashcards

1
Q

What are the two distinct endocrine gland regions found in the adrenal glands?

A

Cortex and the medulla

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2
Q

What are the three steroid hormones that the adrenal glands secrete?

A

Glucocorticoids Mineral corticoids androgens

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3
Q

What are the catecholamines that are secreted by the adrenal glands?

A

Epinephrine and norepinephrine

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4
Q

What are the three layers of the adrenal cortex going from superficial to deep?

A

zona glomerulosa, zona fasciculata, and zona reticularis

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5
Q

What does the adrenal cortex synthesize?

A

aldosterone

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6
Q

What are the two chemicals that regulate aldosterone synthesis?

A

Angiotensin II, and K

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7
Q

What are the two glucocorticoids that the zona fasciculata and the zona reticularis secrete?

A

Cortisol and corticosterone

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8
Q

What are the two androgens that the zona fasciculata and the zona reticularis secrete?

A

dehydroepiandosterone (DHEA) and androstenedione

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9
Q

What are the cells in the inner layer of the adrenal glands that synthesize and secrete epi/norepi?

A

Chromaffin cells

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10
Q

What is the zona glomerulosa responsible for synthesizing?

A

Aldosterone

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11
Q

What is the zona fasciculata responsible for synthesizing?

A

cortisol

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12
Q

What is the zona reticularis responsible for synthesizing?

A

Androgens

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13
Q

What is the main function of cortisol?

A

Restoring homeostasis after exposure to stresses

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14
Q

The production of glucocorticoids is controlled by multiple hormones that are synthesized and secreted from where?

A

The HPA axis

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15
Q

What are the components of the HPA axis?

A

Hypothalamus, the anterior pituitary, and the adrenocortical

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16
Q

What is the hormone that causes the release of glucocorticoids in the hypothalamus?

A

Corticotropin-releasing hormone (CRH)

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17
Q

What is the function of CRH? (what does it bind to, what does it cause x2)

A

Binds to, and activates a G-protein on corticotropic cells of the anterior pituitary, causing ACTH secretion and increase production of POMC

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18
Q

What is the function of ACTH once released from the pituitary?

A

Binds to a melanocortin 2 receptor on adrenal cortical cells, to increase steroidogenic enzyme expression and secretion

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19
Q

What type of G protein is found on the corticotroph cells that cause the release of ACTH? What is the pathway associated with this?

A

G-alpha, causes PKA and Ca increase, causing preformed ACTH release

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20
Q

ACTH is a proteolytic cleavage product of what?

A

the larger precursor protein called pro-opiomelanocortin (POMC)

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21
Q

What is the receptor that ACTH binds to on the surface of adrenal cortex? What G protein?

A

MC2R G-alpha

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22
Q

When ACTH binds to MC2R on the adrenal cortex, what does this cause? (2)

A

PKA to increase, which activates cholesterol side chain cleavage enzyme, and increases cholesterol transport into the cell

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23
Q

What is the first step of steroid production? What is the protein needed for this?

A

Transport of cholesterol into the mito STAR protein

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24
Q

What is the protein that converts cholesterol in the mitochondria to pregnenolone?

A

p450scc

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25
Q

What is the first, and rate limiting step of steroid synthesis? (substrate, enzyme, and product)

A

Cholesterol conversion to pregnenolone via the p450scc enzyme

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26
Q

Draw out the mineralocorticoid, glucocorticoids, and androgen synthesis pathways.

A
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27
Q

A defect in the 17alpha enzyme leads to a build up of what product?

A

Aldosterone

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28
Q

A defect in the 21-hydroxylase enzyme leads to a build up of what products?

A

Androgens

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29
Q

What is the major enzyme found in the glomerulosa of the adrenal cortex? What is the enzyme found in the lowest amount?

A

Aldosterone synthase Little 17alpha-hydroxylase

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30
Q

What are the androgens? Where are these produced?

A

DHEA and androstenedione In the reticularis part of the adrenal cortex

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31
Q

What are the two components of aldosterone synthase?

A

18-hydroxylase 18-hydroxydehydrogenase

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32
Q

What is the effect of ACTH on the growth of the adrenal cortex?

A

Increased ACTH causes hypertrophy.

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33
Q

Cortisol and ACTH are released into the blood in what sort of pattern?

A

Pulsatile with fluctuations based on the circadian cycle

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34
Q

When is the highest level of cortisol? Lowest?

A

Highest = when waking Lowest = at bed time

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35
Q

What is the biggest cause of increased ACTH/cortisol?

A

Stress

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36
Q

Free cortisol can freely traverse the cell membrane since it is lipophilic. What happen once it does?

A

Binds to the GR receptor, causing the receptor to dissociate from HSPs.

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37
Q

Where does the GR receptor/cortisol complex go once bound together? What does it then bind to?

A

To the nucleus, dimerizes, and binds to the glucocorticoid response element on DNA

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38
Q

What is the overall effect of the binding of the GR receptor/cortisol complex to the GRE?

A

Either activate or inhibit gene transcription

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39
Q

What is the effect of cortisol on blood glucose levels?

A

Increases

40
Q

What is the effect of cortisol on the immune system?

A

Inhibits

41
Q

What is the effect of cortisol on fibroblast proliferation?

A

Decreased, leading to decrease CT

42
Q

What is the effect of cortisol on bone matrix reabsorption and Ca excretion?

A

Increases

43
Q

What is the effect of cort on muscles?

A

Breaks down into AAs to feed into gluconeogenesis pathway

44
Q

What are the two ways that cort increases blood glucose levels through the liver?

A

Increases gluconeogenesis and glycogenolysis

45
Q

What are the three major effects of cort on skeletal muscle

A
  1. Decreases glucose uptake 2. increases glycogenolysis 3. Increases protein catabolism
46
Q

What is the effect of cort on adipose tissue?

A

Decreases glucose uptake Increases lipolysis

47
Q

What are the two enzymes that cortisol affects to increase glycogenolysis?

A

Increases expression of glycogen synthase Inhibits glycogen phosphorylase

48
Q

How does cort increase cardiac output and blood pressure?

A

Induces expression of receptors for epi and norepi

49
Q

How does cortisol increase the conversion of norepi into epi in the adrenal medulla?

A

Increases expression of the enzyme that does the conversion in the chromaffin cells

50
Q

How does cortisol decrease the production of prostaglandins, leukotrienes, PAF etc?

A

Inhibits phospholipase A2 activity

51
Q

How does cortisol decrease prostaglandin production?

A

Inhibits COX

52
Q

How does cortisol decrease NO production?

A

Inhibits NO synthase

53
Q

How does cortisol suppress cell mediated immunity?

A

Inhibits cytokine production

54
Q

How does cortisol decrease levels of mast cell inflammatory mediators (e.g. histamine and 5HT)?

A

Inhibits mast cell activity and reduction of mast cell numbers

55
Q

What is the effect of cortisol on blood vessels?

A

Vasoconstriction

56
Q

What are the three primary androgens? What can they all be converted into?

A

DHEA, DHEA-S, and androstenedione Converted into Testosterone/estrogens

57
Q

What is the relative contribution of testosterone from the adrenal cortex in the male?

A

Small (<5%)

58
Q

What is the importance of androgen derived testosterone in women?

A

Maintenance of pubic and axillary hair

59
Q

Excess adrenal androgens cause what in men and women?

A

Men = precocious puberty Women = hirsutism

60
Q

How does aldosterone increase BP?

A

Increases volume by decreasing Na secretion and increased K excretion

61
Q

Renin is released by what? What does it do?

A

Release by juxtaglomerular cells. Cleaves angiotensinogen to angiotensin I…aldosterone

62
Q

What is the rxn that ACE catalyzes?

A

Angiotensin I to II

63
Q

What does aldosterone bind to when it enters a renal epithelial cell? What what does this then bind to?

A

Mineralocorticoid receptor (MR) This complex travels to the nucleus, to bind to GRE on DNA

64
Q

What does the MR/aldosterone complex increase the transcription of?

A

ENaC transporter Na/K ATPase

65
Q

What is the function of ENaC transporter?

A

Transports Na from the tubular lumen of the nephron to the lumen of the renal epithelial cell

66
Q

What is the function of the Na/K transporter in the nephron tubule epithelial cell? How does this increase water in the blood?

A

Transports Na into the interstitial fluid in exchange for K. Water follows Na

67
Q

What is the inactive form of cortisol?

A

cortisone

68
Q

What is the enzyme that converts cortisone to cortisol? What is the enzyme for the reverse reaction?

A

11beta-HSD1 goes to cortisol 11beta-HSD2 goes to cortisone

69
Q

Cortisol can bind to the GRE element of the renal tubule epithelial cell’s DNA just as well as aldosterone can. How does the tubule cell get around this issue?

A

Converts cortisol into cortisone

70
Q

What happens to 11beta-HSD2 in cushing’s syndrome? What does this eventually cause?

A

It becomes saturated, eventually causing HTN

71
Q

Is the adrenal medulla innervated by the parasympathetic or sympathetic nervous system? What is the neurotransmitter used in this? What does this neurotransmitter bind to

A

Sympathetic–Ach–binds to chromaffin cells

72
Q

What are the cells in the renal medulla that synthesize and secrete epi/norepi?

A

Chromaffin cells

73
Q

What is the rate limiting step of catecholamine synthesis? What is the enzyme that is involved?

A

Y to DOPA, catalyzed by Tyrosine hydroxylase

74
Q

What is the substance that can inhibit tyrosine hydroxylase?

A

Metyrosine

75
Q

What is the enzyme that converts Epinephrine to Norepinephrine?

A

phenylethanolamine-N-methyltransferase (PNMT)

76
Q

What is epinephrine metabolized to? Norepi?

A

Epi = Metanephrine Norepi = Normetanephrine

77
Q

What are the receptors of epi/norepi? What are they coupled to?

A

Adrenergic receptors (alpha and beta) G protein coupled

78
Q

What are the subtypes of the alpha and beta adrenergic receptors that epi and norepi use?

A

a1, a2, B1, B2, B3

79
Q

Which are more strongly activated by norepi, alpha or beta adrenergic receptors?

A

Alpha

80
Q

What is the chemical that mediates the short term stress response? Long term?

A

Short = epi/norepi Long = ACTH (mineralocorticoids and glucocorticoids)

81
Q

Moon facies + thick neck + growth retardation + fat trunk + abdo and thin extremities = what disease?

A

Cushings

82
Q

Why can hypercortisolism cause hypokaleemia and HTN?

A

Increases aldosterone, (which leads to increase in Na/K pumps on renal epithelial cells, as well as ENaC pores).

83
Q

What is Cushing’s “disease”?

A

Pituitary hypersecretion of ACTH

84
Q

What happens to ACTH levels if you have an adrenal adenoma? What does this adenoma cause?

A

Lowers ACTH but causes cushing’s syndrome

85
Q

What are the four ways Cushing’s syndrome can result?

A
  1. Pituitary hyper ACTH secretion 2. Adrenal adenoma 3. Ectopic ACTH production 4. Iatrogenic glucocorticoid administration
86
Q

What happens to [ACTH] with iatrogenic cushing’s?

A

Goes down

87
Q

What is the underlying cause of Addison’s disease?

A

Destruction of the adrenal cortex via autoimmune. This decreases cort and glucocorticoids

88
Q

What happens to [ACTH] in primary adrenal insufficiency or Addison’s disease? Why?

A

increases since there is no Cort to feed back

89
Q

Why do you get hypoglycemia in Addison’s disease?

A

Low Cort

90
Q

Why do you get hypotension in Addison’s disease?

A

Less aldosterone

91
Q

Why do you get hyperkalemia with Addison’s disease?

A

Less cort means less aldosterone means less K excretion

92
Q

Why is hyperpigmentation seen in Addisons?

A

lower POMC

93
Q

What are the two possible causes of secondary adrenal insufficiency?

A

Pituitary disease or hypothalamus disease

94
Q

What is the [CRH] for hypothalamic causes of adrenal insufficiency? [ACTH]?

A

both lower

95
Q

What is the [CRH] for pituitary causes of adrenal insufficiency? [ACTH]?

A

increased CRH lower ACTH

96
Q

What is the one function that is mostly preserved with secondary adrenal insufficiency?

A

Aldosterone secretion

97
Q

What is the enzymatic deficiency of congential adrenal hyperplasia? What does this lower the [c] of?

A

21-hydroxylase, leading to decreased aldosterone

Physiology (75 decks)

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