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the adrenal axis Flashcards

1
Q

what does the foetal adrenal gland synthesise?

A

synthesises 16-hydroxy-androstendeiol which is converted into oestriol by P450 in the placenta

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2
Q

what are the metabolic effects of cortisol

A

increases plasma glucose by:

  • inhibiting insulin mediated glucose deposition
  • increase hepatic gluconeogenesis
  • increase availability of gluconeogenic substrates (e.g. glycerol and free amino acids)
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3
Q

what is the effect of cortisol on the heart?

A

positive ion tropic and leads to abnormal ECGs

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4
Q

what is the effect of cortisol on the kidney?

A

increases renal blood flow and GFR

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5
Q

what is the effect of cortisol on fibroblasts?

A

inhibits their proliferation and collagen formation around bV this increases bruising and leads to impaired wound healing

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6
Q

why is cortisol important for the young?

A

because cortisol is secreted in the last trimeter of pregnancy and it is a surfactant reducing the surface tension within the lungs

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7
Q

what is the affect of cortiol on calcium?

A

it increases plasma calcium levels by breaking down bone

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8
Q

why does excess cortisol cause hyperglycaemia?

A

because increases gluconeogenesis and glycogenolysis also increases protein catabolism

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9
Q

how does excess cortisol effect body fat distribution?

A

lipolysis in the extremities due to activation of HSL. and lipogenesis centrally causing central adiposity. this results in a plethoric face, a buffalo hump

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10
Q

how does excess cortisol effect body fat distribution?

A

lipolysis in the extremities due to activation of HSL. and lipogenesis centrally causing central adiposity. this results in a plethoric face, a buffalo hump

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11
Q

what are the effects of excess cortisol on the immune system?

A 
anti-inflammatory (PLA-2 inhibition) 
lymphatic/thymus involution 
antagonise cytokine action 
gastric ulceration 
osteoporosis
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12
Q

why does cortisol cause hyperandrogenism, and why is it more potent in females?

A

because it cases excess DHEA production, it is more potent in women because it forms a significant amount of their tesotersterone level, in males DHEA levels are swapmed

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13
Q

how does excess cortisol effect electrolyte and fluid balance?

A
  • causes hypokalaemia, and anti-natriuses

- causes hyervolaemic hypertension

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14
Q

what hormones are involved in our acute stress response?

A

catecholamines

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15
Q

what hormone is responsible of our chronic stress response?

A

cortisol

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16
Q

what is the old name of C11B1?

A

11-beta hydroxylase (involved in hydroxylating deoxycortisol)

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17
Q

what is the old name of C11B2?

A

aldosterone synthetase (makes aldosterone from hydroxy-corticosterone)

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18
Q

why does cortisol cause hyperandrogenism, and why is it more potent in females?

A

because it cases excess DHEA production, it is more potent in women because it forms a significant amount of their tesotersterone level, in males DHEA levels are swapmed

this causes female hermaphermatodism and also it is the main source of oestrogen (as a substate) in post-menapausal women

in women excess DHEA is responsible for Adrenarche

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19
Q

what is the old name of C11B2?

A

aldosterone synthetase (makes aldosterone from hydroxy-corticosterone)

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20
Q

what is the rate limiting step in steroid synthesis?

A

cholesterol side chain cleavage enzyme

21
Q

when is ACTH tested?

A

when you suspect Addison’s disease

22
Q

what is the purpose of the dexamethasone suppression test?

A

it is used to define a glucocorticoid excess, particularly helpful in diagnosing cushing’s syndrome

23
Q

what is the purpose of the CRH test?

A

it is used to differentiate between ac ectopic source of ACTH tumour and an anterior pituitary tumour.

anterior pitutiary tumours in response to CRH will cause an excess secretion of ACTH and Cortisol

in an ectopic tumour: there should be no change in ACTH or cortisol levels

24
Q

what is the definitive diagnosis for Cushing’s disease?

A

using inferior petrosal blood: a ratio of ACTH to peripheral ACTH is taken. a ratio of greater than two is definitive diagnosis. the CRH test can also be given to stimulate an even more exaggerated response

25
what steroids are affected in Addisson's disease?
cortisol and DHEA and aldosterone
26
What steroids are affected in ACTH defect?
only those affected by the ACTH axis: cortisol and DHEA
27
Why is there hyperplasia in congenital adrenal hyperplasia
the loss of function mutations or the lack of expression of steredogeneic enzymes means that no cortisol is being produced to feedback on the ACTH axis, and so more ACTH is produced and this causes hyperplasia
28
what is the common feature to both salt wasting and salt sparring CAH? and why?
the common feature is DHEA which leads to female visualisation. this is because Excess ACTH drive is found due to the lack of negative feedback
29
what is the common feature to both salt wasting and salt sparring CAH? and why?
the common feature is DHEA which leads to female visualisation. this is because Excess ACTH drive is found due to the lack of negative feedback
30
what causes salt wasting CAH?
mutations in CP21
31
what causes salt sparring CAH?
MUTATIONS in C11B1 this can cause malignant hypertension
32
why does addison's cause hepatic glycogen depletion?
this is because cortisol stimulates hepatic gluconeogenesis (thereby increasing plasma glucose) - it increases hepatic glycogen as a glucose reverse for the future, and cortisol increases expression of glycogen synthetase.
33
what is the cause of malignant hypertension in salt sparring CAH?
• DOC is produced in excess o DOC posses mineralocorticoid activity but no glucocorticoid activity o It is the precursor for aldosterone synthesis • Lack of aldosterone and cortisol raise ACTH drive thus more DOC is produced • Normal feedback mechanisms
34
what causes hyperglycaemia in cushing's syndrome
• Caused by elevated glucocorticoids o Inhibit IMGD o Spare glucose metabolism o Increase gluconeogenesis
35
what causes the hypokaelemia in the adrenal axis?
Hypokalemia: • Caused by elevated mineralocorticoids • Elevated glucocorticoids also contribute
36
what causes increased gluconeogenesis?
* Glucocorticoids * Increased expression of gluconeogenic enzymes in the liver * Increased availability of glycerol and gluconeogenic amino acids
37
what causes acne?
* Elevated adrenal androgens | * Increased production of sebaceous secretions
38
what causes immune suppression?
• Elevated glucocorticoids • Involution of thymus and lymphatic tissue • Induction of lipocortin expression inhibits PLA2 o Suppresses inflammatory mediators
39
what causes osteoporosis?
• Elevated glucocorticoids • Increased catabolism of bone o They also inhibit fibroblasts number and differentiation o Therefore slow down bone formation
40
what cause anti-natriuses?
• Elevated mineralocorticoids
41
what causes insulin resistance?
• Elevated glucocorticoids • Antagonises insulin actions o Directly and indirectly
42
what causes increased bruising?
* Elevated glucocorticoids * Less muscle and adipose to protect blood vessels * Suppressed proliferation of fibroblasts * Impaired collagen synthesis
43
what causes hirsutism
• Elevated adrenal androgens | o Increased stimulation of androgen dependant hair follicles
44
what causes gastric ulceration?
• Elevated glucocorticoids • Acid attack on gastric mucousa inhibited by prostaglandins • Prostaglandin synthesis inhibited by glucocorticoids o Glucocorticoids increase Annexin 1 expression
45
what causes hypervolemia hypertension?
* Elevated mineralocorticoids | * And to some extent glucocorticoids
46
what causes cliteromegaly?
• Elevated adrenal androgens o This changes female external genital o Resulting in external male appearing genitals in XX individuals • Differentiation of genital tubercle into glans • Labial fusion • DHEA → testosterone → 5aDHT
47
what is Nelson's syndrome?
this is an iatrogenic condition, causing a pituitary tumour secreting ACTH due to a bilateral adrenectolmy - this si increasingly rare - because this type of surgery no longer preformed
48
what are some of the signs of Conn's syndrome?
hypokalaemia, low renin, an T wave on the ECG | adrenal mass on CT scans and elevated aldosterone levels
49
what are the symptoms of Conn's sdnrome?
fatigue, headache, high blood pressure, intermittent paralysis, muscle weakness and numbness

Endocrinology (6 decks)

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