The Adrenal Gland Flashcards Preview

Regulatory Physiology and Pharmacology > The Adrenal Gland > Flashcards

Flashcards in The Adrenal Gland Deck (107):
1

What is the adrenal gland?

a hybrid gland consisting of a cortex and a medulla

2

What is important about the hormones of the adrenal gland?

regulators of metabolism and adaptation to stress

3

What is cortisol?

glucocorticoid which increases plasma glucose levels

4

What is aldosterone?

mineralocorticoid promotes salt and water retention by the kidney

5

What else is secreted by the adrenal cortex?

weak androgens which can be converted to testosterone

6

What are the products of chromaffin cells?

epinephrine but also produces small amounts of norepinephrine

7

What are steroid hormones derived from?

cholesterol - different ring structures and side chains

8

What is the common features of steroid hormones?

lipid soluble so are freely permeable

9

How are steroid hormones are carried in the blood ?

complexed to binding globulins - corticosteroid binding globulin binds cortisol

10

Where are the enzymes that produce steroids from cholesterol?

in the mitochondria and smER

11

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

cellular synthesis of cholesterol from acetate
LDL -> esterified cholesterol from LDL droplets inside the cell

12

What is the rate limiting step in steroidogenesis?

the transport of free cholesterol from the cytoplasm to the mitochodria

13

How is cholesterol carried into the mitochondria?

Steroidgenic Acute Regulatory Protein (StAR)

14

What is cholesterol converted to in the inner membrane?

pregnenolone by CYP450scc -side chain cleavage aka desmolase

15

Where does cholesterol conversion occur?

in the adrenal, ovary and testis

16

What converts pregnenolone to 17a-hydroxypregnenolone?

CYP17

17

What converts pregnenolone and pregesterone to mineralocorticoids?

CYP11B2

18

Where is CYP17 found?

not in glomerulosa

19

Where is CYP11B2 found?

only in the glomerulosa

20

What is synthesised in the fasiculata?

cortisol

21

Which enzyme esterifies free cholesterol?

acyl coA cholesterol transferase

22

Which enzyme turns lipid droplets back into cholesterol?

hormone sensitive lipase

23

What increases the activity of hormone sensitive lipase?

ACTH

24

How many reactions modify cholesterol to cortisol?

5

25

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

CYP11A1
inner mitochondrial membrane

26

How is the activity of StAR increased?

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

27

How is cortisol predominantly transported in the blood?

CBG - 90%
albumin - 5-7%

28

What does the unbound form of cortisol do?

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

29

What does the liver conjugate cortisol with?

gluconoride or sulfate

30

What is the circulating half life of cortisol?

70mins

31

How does cortisol act?

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

32

What happens to GR in the absence of cortisol?

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

33

What happens to GR in the presence of cortisol?

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

34

How is c-GR complex turned off?

phosphorylation and nuclear export or degradation of the GR

35

How is cortisol inactivated?

by 11b-HSD2

36

Why would cortisol be inactivated?

to prevent it binding and activating MR

37

What is the enzyme that activates cortisol?

11b-HSD1

38

Where is 11bHSD1 found?

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

39

What can happen with natural black liquorice?

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

40

What are the actions of cortisol essential for?

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

41

What does cortisol stimulate?

protein and triglyceride catabolism
gluconeogenesis in the liver

42

What does cortisol inhibit?

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

43

How is cortisol secretion regulated by the HP-axis?

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

44

What happens if there is no ACTH?

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

45

What happens in excess ACTH?

enlarged adrenals, excess steroids

46

What does adrenal hyperplasia do in men and women?

women - virilism, hirsutism, clitoral hyperplasia
men - precocious puberty

47

What causes adrenal hyperplasia?

21-hydroxylase deficiency

48

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

ACTH might be used to stimulate androgen production pathway

49

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

dependent - pituitary tumour - Cushings disease
independent - adrenal tumour

50

What are the 2 primary consequences of Cushings syndrome?

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

What is Addisons disease?

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

52

What are the symptoms of addisons disease?

over production of ACTH
skin hyperpigmentation

53

What are the glucocorticoid deficiency symptoms?

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

54

What are the mineralocorticoid deficiency symptoms?

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

55

What does aldosterone govern?

EC volume due to action on Na retention

56

Where is aldosterone produced?

zona glomerulosa

57

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

ADH and aldosterone

58

What enzyme converts cholesterol to aldosterone?

aldosterone synthase

59

What limits the rate of Aldosterone secretion?

there is no storage pool of the hormone

60

What stimulates the production of aldosterone?

ACTH, EC K, and angiotensin II

61

How much aldosterone is free in the plasma?

37%

62

What is aldosterone bound to in the plasma?

GBG and albumin

63

Where does aldosterone act?

mainly kidney
colon, salivary glands, sweat

64

How does aldosterone act?

binds mineralocorticoid receptor and regulates gene transcription

65

What ensures cortisol does not activate the MR?

11b-HSD2

66

What does aldosterone stimulate transcription of?

ROMK channel
ENaC
Na-K pump
SGK-1

67

What is the function of the ROMK?

increases K secretion on apical membrane

68

What is the function of ENac?

brings Na into the cell on the apical membrane

69

What is the function of the Na-K pump?

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

70

What is the function of SGK-1 expression?

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

71

What can loss of aldosterone result in?

hyperkalaemia, hypotension

72

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

3L change in ECV

73

How is aldosterone regulated by Na and water levels?

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

What does Ca stimulate in glomerulosa cells?

production of P450scc
delivery of cholesterol
aldosterone synthase

75

What other two systems increase and regulate aldosterone synthesis?

High EC K+
ACTH

76

How does BP regulate aldosterone synthesis?

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

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

cortisol inhibits neuronal differentiation

78

What does cortisol induce in the chromaffin cells?

the expression of PNMT which converts norepinephrine to epinephrine

79

where are adrenal medullary catecholamines secreted?

into the blood where they act as hormones

80

What does ACTH stimulate in the adrenal medulla?

the conversion of tyrosine to DOPA

81

What enzyme converts tyrosine to DOPA?

tyrosine hydroxylase

82

What is DOPA converted to and by what?

dopamine by amino acid decarboxylase

83

How is dopamine stimulated to convert to norepinephrine?

ACTH stimulates dopamine b-hydroxylase

84

Where does norepinephrine go?

diffuses out of the granule

85

Where does epinephrine go?

back to the granule by vesicular monoamine transporters VMATS

86

What is epinephrine stored in the chromaffin granule with?

ATP, Ca, chromogranins

87

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

all of the epinephrine is derived from the medulla
only 30% of circulating norepinephrine is derived from the medulla

88

Where does the rest of the norepinephrine come from?

the postganglionic sympathetic nerve terminals

89

Where does the rest of the norepinephrine come from?

the postganglionic sympathetic nerve terminals

90

Where are the autonomic centres that initiate the sympathetic response?

hypothalamus and brain stem

91

Where do the hypothalamus and brain stem recieve inputs from?

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

92

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

various forms of stress, including exercise, hypoglycaemia and surgery

93

What is the chemical signal for catecholamine release?

ACh -> nAChR on the chromaffin cells

94

What enzymes does ACh increase the rate of?

tyrosine hydroxylase
dopamine b-hyrdoxylase
exocytosis of chromaffin granules

95

How does cortisol regulated catecholamine secretion?

maintaining adequate expression of PNMT

96

what are the primary enzymes involved in degrading catecholamines?

MAO - neuronal mitochondria
COMT

97

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

methylation to metanephrine and metanorepinephrine

98

What does MAO convert metanephrine to?

VMA - vanillylmandelic acid

99

What does the liver and gut do to metanephrine?

conjugates them to sulfate or glucuronide

100

Where is epinephrine more potent than norepinephrine?

the liver where it activates b2 increaseing cAMP

101

where do catecholamines decrease cAMP?

pancreatic b cells on a2

102

Where do catecholamines increase IP3 and DAG?

a1 on vascular smooth muscle

103

Where are b1 and b3 found?

heart and adipose tissue respectively

104

What are the physiologic actions of catecholamines?

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

What is pheochromocytoma?

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

106

What does pheochromocytoma cause?

sudden hypertension
headaches
episodes of sweating
anxiousness
tremor
glucose intolerance

107

How is pheochromocytoma diagnosed?

urinary catecholamines are detected for diagnosis