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Regulatory Physiology and Pharmacology > The Adrenal Gland > Flashcards

The Adrenal Gland Flashcards

1
Q

What is the adrenal gland?

A

a hybrid gland consisting of a cortex and a medulla

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2
Q

What is important about the hormones of the adrenal gland?

A

regulators of metabolism and adaptation to stress

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3
Q

What is cortisol?

A

glucocorticoid which increases plasma glucose levels

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4
Q

What is aldosterone?

A

mineralocorticoid promotes salt and water retention by the kidney

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5
Q

What else is secreted by the adrenal cortex?

A

weak androgens which can be converted to testosterone

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6
Q

What are the products of chromaffin cells?

A

epinephrine but also produces small amounts of norepinephrine

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7
Q

What are steroid hormones derived from?

A

cholesterol - different ring structures and side chains

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8
Q

What is the common features of steroid hormones?

A

lipid soluble so are freely permeable

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9
Q

How are steroid hormones are carried in the blood ?

A

complexed to binding globulins - corticosteroid binding globulin binds cortisol

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10
Q

Where are the enzymes that produce steroids from cholesterol?

A

in the mitochondria and smER

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11
Q

What are the sources of free cholesterol in the cell is maintained relatively constant?

A

cellular synthesis of cholesterol from acetate

LDL -> esterified cholesterol from LDL droplets inside the cell

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12
Q

What is the rate limiting step in steroidogenesis?

A

the transport of free cholesterol from the cytoplasm to the mitochodria

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13
Q

How is cholesterol carried into the mitochondria?

A

Steroidgenic Acute Regulatory Protein (StAR)

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14
Q

What is cholesterol converted to in the inner membrane?

A

pregnenolone by CYP450scc -side chain cleavage aka desmolase

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15
Q

Where does cholesterol conversion occur?

A

in the adrenal, ovary and testis

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16
Q

What converts pregnenolone to 17a-hydroxypregnenolone?

A

CYP17

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17
Q

What converts pregnenolone and pregesterone to mineralocorticoids?

A

CYP11B2

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18
Q

Where is CYP17 found?

A

not in glomerulosa

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19
Q

Where is CYP11B2 found?

A

only in the glomerulosa

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20
Q

What is synthesised in the fasiculata?

A

cortisol

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21
Q

Which enzyme esterifies free cholesterol?

A

acyl coA cholesterol transferase

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22
Q

Which enzyme turns lipid droplets back into cholesterol?

A

hormone sensitive lipase

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23
Q

What increases the activity of hormone sensitive lipase?

A

ACTH

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24
Q

How many reactions modify cholesterol to cortisol?

A

5

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25
Q

What is the first enzyme in the modification of cholesterol to cortisol and where is it located?

A

CYP11A1

inner mitochondrial membrane

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26
Q

How is the activity of StAR increased?

A

ACTH stimulates Gs -> cAMP-> PKA which phosphorylates StAR

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27
Q

How is cortisol predominantly transported in the blood?

A

CBG - 90%

albumin - 5-7%

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28
Q

What does the unbound form of cortisol do?

A

exerts its effects on tissues and feedsback on the pituitary and hypothalamus

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29
Q

What does the liver conjugate cortisol with?

A

gluconoride or sulfate

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30
Q

What is the circulating half life of cortisol?

A

70mins

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31
Q

How does cortisol act?

A

through glucocorticoid receptor which bind the Glucocorticoid response Element and regulates gene transcription

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32
Q

What happens to GR in the absence of cortisol?

A

resides in cytoplasm in complex with chaperones including heat shock protein 90 and cyclophillins

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33
Q

What happens to GR in the presence of cortisol?

A

moves to the nucleus and binding GRE near basal promotors of cortisol regulated genes
recruits co-activator or co-repressor proteins followed by covalent modification of chromatin

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34
Q

How is c-GR complex turned off?

A

phosphorylation and nuclear export or degradation of the GR

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35
Q

How is cortisol inactivated?

A

by 11b-HSD2

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36
Q

Why would cortisol be inactivated?

A

to prevent it binding and activating MR

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37
Q

What is the enzyme that activates cortisol?

A

11b-HSD1

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38
Q

Where is 11bHSD1 found?

A

in cells that express the GR including liver, adipose, skin and CNS

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39
Q

What can happen with natural black liquorice?

A

inactivates 11b-HSD2 which results in MR activation by cortisol, Na retention, increased BP and muscle spasms

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40
Q

What are the actions of cortisol essential for?

A

gluconeogenesis
suppression of inflammatory and immune responses
modulation of CNS function
vascular responsiveness to catecholamines
surviving fasting

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41
Q

What does cortisol stimulate?

A

protein and triglyceride catabolism

gluconeogenesis in the liver

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42
Q

What does cortisol inhibit?

A

glucose uptake by the body - goes to brain
elevates blood glucose - diabetogenic
bone formation
non-essential function i.e. growth

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43
Q

How is cortisol secretion regulated by the HP-axis?

A

CRH and ADH secretion are controlled by the supraoptichiasmatic nucleus and retina - circadian rhythm which thus regulates ACTH and cortisol

44
Q

What happens if there is no ACTH?

A

fasciculata and reticularis atrophy and no cortisol production - dependent on exogenous glucocorticoids

45
Q

What happens in excess ACTH?

A

enlarged adrenals, excess steroids

46
Q

What does adrenal hyperplasia do in men and women?

A

women - virilism, hirsutism, clitoral hyperplasia

men - precocious puberty

47
Q

What causes adrenal hyperplasia?

A

21-hydroxylase deficiency

48
Q

What happens when the body cannot cope with the demand for cortisol?

A

ACTH might be used to stimulate androgen production pathway

49
Q

What is the difference between ACTH independent and dependent Cushings Syndrom?

A

dependent - pituitary tumour - Cushings disease

independent - adrenal tumour

50
Q

What are the 2 primary consequences of Cushings syndrome?

A

Salt and Water retention with renal loss of K - results in moon face and cardiac hypertrophy due to increased BP and peripheral oedema and glucocorticoid induced diabetes
Catabolism causes muscle wasting, fat accumulation, osteoporosis, kyphosis, buffalo hump, fracture, ulcered skin and poor wound healing§

51
Q

What is Addisons disease?

A

a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hromones

52
Q

What are the symptoms of addisons disease?

A

over production of ACTH

skin hyperpigmentation

53
Q

What are the glucocorticoid deficiency symptoms?

A

hypglycaemia, hypotension, changes in mood, muscle weakness, anemia, decreased GI motility and appetite

54
Q

What are the mineralocorticoid deficiency symptoms?

A

loss of Na, craving salt, loss of fluids and retention of K, hypotension, muscle fatigue and pain due to increased EC K+

55
Q

What does aldosterone govern?

A

EC volume due to action on Na retention

56
Q

Where is aldosterone produced?

A

zona glomerulosa

57
Q

What are the two integrated systems for balancing salt and water?

A

ADH and aldosterone

58
Q

What enzyme converts cholesterol to aldosterone?

A

aldosterone synthase

59
Q

What limits the rate of Aldosterone secretion?

A

there is no storage pool of the hormone

60
Q

What stimulates the production of aldosterone?

A

ACTH, EC K, and angiotensin II

61
Q

How much aldosterone is free in the plasma?

A

37%

62
Q

What is aldosterone bound to in the plasma?

A

GBG and albumin

63
Q

Where does aldosterone act?

A

mainly kidney

colon, salivary glands, sweat

64
Q

How does aldosterone act?

A

binds mineralocorticoid receptor and regulates gene transcription

65
Q

What ensures cortisol does not activate the MR?

A

11b-HSD2

66
Q

What does aldosterone stimulate transcription of?

A

ROMK channel
ENaC
Na-K pump
SGK-1

67
Q

What is the function of the ROMK?

A

increases K secretion on apical membrane

68
Q

What is the function of ENac?

A

brings Na into the cell on the apical membrane

69
Q

What is the function of the Na-K pump?

A

takes Na into the blood and K into the cell on the basolateral membrane

70
Q

What is the function of SGK-1 expression?

A

enhances ROMK, ENaC and Na-K pump
decreases degradation fo ENac
serine/threonine kinase

71
Q

What can loss of aldosterone result in?

A

hyperkalaemia, hypotension

72
Q

What sort of change does a 2% change in Na excretion cause?

A

3L change in ECV

73
Q

How is aldosterone regulated by Na and water levels?

A 
Feedback through the RAS system
AngII binds to AT1 receptor
Gaq -> PLC -> DAG and IP3
Ca increases depolarising cell and increasing Ca further
Ca stimulates
production of P450scc
delivery of cholesterol
aldosterone synthase
74
Q

What does Ca stimulate in glomerulosa cells?

A

production of P450scc
delivery of cholesterol
aldosterone synthase

75
Q

What other two systems increase and regulate aldosterone synthesis?

A

High EC K+

ACTH

76
Q

How does BP regulate aldosterone synthesis?

A

low BP is detected by baroreceptors in the kidney which release renin from Juxtaglomerular cells and cause activation of sympathetic fibers and innervate JG cells through b1-adrenergic receptors

77
Q

what prevents chromaffin cells from developing into post-ganglionic sympathetic neurons?

A

cortisol inhibits neuronal differentiation

78
Q

What does cortisol induce in the chromaffin cells?

A

the expression of PNMT which converts norepinephrine to epinephrine

79
Q

where are adrenal medullary catecholamines secreted?

A

into the blood where they act as hormones

80
Q

What does ACTH stimulate in the adrenal medulla?

A

the conversion of tyrosine to DOPA

81
Q

What enzyme converts tyrosine to DOPA?

A

tyrosine hydroxylase

82
Q

What is DOPA converted to and by what?

A

dopamine by amino acid decarboxylase

83
Q

How is dopamine stimulated to convert to norepinephrine?

A

ACTH stimulates dopamine b-hydroxylase

84
Q

Where does norepinephrine go?

A

diffuses out of the granule

85
Q

Where does epinephrine go?

A

back to the granule by vesicular monoamine transporters VMATS

86
Q

What is epinephrine stored in the chromaffin granule with?

A

ATP, Ca, chromogranins

87
Q

What is the difference between the needs for epinephrine and norepinephrine?

A

all of the epinephrine is derived from the medulla

only 30% of circulating norepinephrine is derived from the medulla

88
Q

Where does the rest of the norepinephrine come from?

A

the postganglionic sympathetic nerve terminals

89
Q

Where does the rest of the norepinephrine come from?

A

the postganglionic sympathetic nerve terminals

90
Q

Where are the autonomic centres that initiate the sympathetic response?

A

hypothalamus and brain stem

91
Q

Where do the hypothalamus and brain stem recieve inputs from?

A

the cerebral cortex, limbic system and other regions of the hypothalamus and brain stem

92
Q

What are the general signals which stimulate secretion of epinephrine and norepinephrine?

A

various forms of stress, including exercise, hypoglycaemia and surgery

93
Q

What is the chemical signal for catecholamine release?

A

ACh -> nAChR on the chromaffin cells

94
Q

What enzymes does ACh increase the rate of?

A

tyrosine hydroxylase
dopamine b-hyrdoxylase
exocytosis of chromaffin granules

95
Q

How does cortisol regulated catecholamine secretion?

A

maintaining adequate expression of PNMT

96
Q

what are the primary enzymes involved in degrading catecholamines?

A

MAO - neuronal mitochondria

COMT

97
Q

What is the fate of catecholamines in non-neuronal tissues?

A

methylation to metanephrine and metanorepinephrine

98
Q

What does MAO convert metanephrine to?

A

VMA - vanillylmandelic acid

99
Q

What does the liver and gut do to metanephrine?

A

conjugates them to sulfate or glucuronide

100
Q

Where is epinephrine more potent than norepinephrine?

A

the liver where it activates b2 increaseing cAMP

101
Q

where do catecholamines decrease cAMP?

A

pancreatic b cells on a2

102
Q

Where do catecholamines increase IP3 and DAG?

A

a1 on vascular smooth muscle

103
Q

Where are b1 and b3 found?

A

heart and adipose tissue respectively

104
Q

What are the physiologic actions of catecholamines?

A 
fatty acids broken down
blood glucose increased
HR and force increases
digestion slows
respiratory passages dilate
bronchiole dilation occurs
BP goes up from vasoconstriction
105
Q

What is pheochromocytoma?

A

uncommon tumour caused by hyperlasia of the adrenal medulla or other chromaffin tissues

106
Q

What does pheochromocytoma cause?

A 
sudden hypertension
headaches
episodes of sweating
anxiousness
tremor
glucose intolerance
107
Q

How is pheochromocytoma diagnosed?

A

urinary catecholamines are detected for diagnosis

Regulatory Physiology and Pharmacology (14 decks)

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