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37 - Adrenals Flashcards

1
Q

Embryological origin of the adrenals, gonads and kidneys

A

Embryonic ridge

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2
Q

What does the embryonic ridge spilt into

A

Adrenogonadal primordium
and neural crest cells
- forms foetal adrenal which has 4 zones

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3
Q

Zones of the adrenals from outermost to inner

A

Zona glomerulosa
Zona fasciculata
Zona reticularis

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4
Q

Where are the adrenals and what are they made up of

A

Above the kidney

Made up of adrenal cortex and medulla

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5
Q

Blood supply of the adrenal gland

A

Flows in from the capsule and flows centrally
Blood is exposed to cortisol produced in zona fasciculata
Blood supply into adrenal medulla has been exposed to steroids

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6
Q

Hormone from Zona glomerulosa + receptor

A

Adosterone

CYPIIB2

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7
Q

Hormone from Zona fasciculata + receptor

A

Cortisol

CYPIIBI

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8
Q

Hormone from Zona reticularis + receptor

A

Testosterone

CYPI7AI

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9
Q

What is the function of aldosterone

A

Vasoconstriction
K+ Secretion
Na+ re absorption
= Increases BV

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10
Q

Hyperaldosterism

A

Low K+
High BP
Metabolic Alkalosis
Hypernatremia

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11
Q

Where is the mineralcorticoid receptor

A

In nucleus almost everywhere

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12
Q

What does the mineralcorticoid receptor bind to

A

Cortisol and aldosterone

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13
Q

What converts cortisol to cortisone in the kidney

A

11BHS2

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14
Q

Why is cortisol converted to cortisone

A

As more cortisol in the blood

Cortisone doesn’t active the receptor and allows for aldosterone to bind too

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15
Q

What does aldosterone bind to in the kidney

A

Mineralcorticoid receptor in principle cell in distal convulated tubule

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16
Q

What does aldosterone do in the kidney DCT

A

Activate Na+/K+ ATPse
Upregulates ENaC so Na reabsorbed and K+ excreted
Cl- absorbed to maintain neutrality

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17
Q

What does aldosterone do in in the intercalated cells (A and B cells)

A

Binds to the MR receptor
Activates Na+./K+ pump
Activate H+/K+ ATPase causes loss of H+ –> acid urine and alkalotic blood

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18
Q

Conn’s Syndrome

A

Primary hyperaldosterism

  • Hypertension
  • Suppressed plasma renin activity
  • increased aldosterone secretion
  • Aldosterone producing adenoma, bilateral adrenal hyperplasia
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19
Q

How do you diagnose Conn’s syndrome

A 
Aldosterone:renin ration
Saline suppression test(to try and suppress aldosterone)
CT adrenal
Adrenal venous sampling
Metomidate PET
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20
Q

What can cause glucocorticoid remediable aldosteronism

A

Aldosterone synthase and 11 B hydroxylase can cross over and form a mutated gene
ACTH activates promotor of 11B hydroxylase and increases aldosterone

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21
Q

What is glucocorticoid remediable aldosteronism

A

Low potassium
High BP
Met alk

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22
Q

How do you treat GRA

A

Steroids

Can suppress ACTH and so suppresses aldosterone

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23
Q

What does liquorice inhibit and what does it do

A

11BHSD2

Stops activation of cortisol

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24
Q

How can cortisol cause hyperaldosterism

A

Cortisol binds to MR

Can lead to syndrome of apparent mineralocorticoid excess

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25
Liddle syndrome
Mutation which increases ENaCs Hypertension, hypokalaemia, metabolic acidosis Low aldosterone
26
What does the HPA axis respond to
Stress
27
Where is corticotropin-releasing hormone released
Hypothalamus
28
Where is ACTH released and what does it bind to
Released from anterior pituitary Binds to MC2R in adrenal gland Glucocorticoids released
29
Feedback loops int the HPA axis
Cortisol inhibits production of CRH and ACTH ACTH inhibits CRH ACTH inhibits its own production
30
What do steroids activate
Hippocampus which inhibits hypothalamus
31
What does the immune response activate
Hypothalamus to release CRH and is inhibited by glucocorticoids
32
What activates and inhibits the hypothalamus
Activates - stress, catecholamines, ang II, ghrelin | - inhibits - Opiates, ANP and oxytocin
33
What inhibit and activates ACTH
CRIF inhibits | Ang II and cytokines activate
34
When is cortisol highest and lowest
Highest as you wake up | Lowest when you are asleep
35
How do we respond to starvation, infection and hypotension
Starvation - Tissue breakdown for fuel Infection - Immunosuppression Hypotension - increase BP
36
Cushings syndrome
Excess cortisol
37
Symptoms of cushing's syndrome
``` Dorsal fat pad - buffalo hump Enlarged heart - high BP Obesity Muscle weakness Osteoporosis Easy bruising Skin ulcers Swollen face and abdomen ```
38
Causes of cushings
iatrogenic Corticotroph adenoma of the pituitary Ectopic ACTH secreting neuroendocrine tumour Bilateral adrenal hyperplasia
39
How do diagnose cushings
Overnight dexamethasone suppression test 24 hour urine free cortisol 0.5mg dexamethasone every 6 hours for 48 hours, Cortisol day curve plus midnight sleeping cortisol
40
Imaging to diagnose cushings syndrome
MRI pituitary, CT adrenals, Inferior petrosal sinus sampling, NM: Octreotide uptake scan
41
Pituitary treatment for cushings syndrome
Transsphenoidal surgery | External beam radiotherapy
42
Adrenal treatment for Cushing's syndrome
Adrenalectomy | Metyrapone/ketoconazole/etomidate
43
Addison's disease
Low levels of corticosteroids
44
Causes of addisons disease
Primary adrenal failure - autoimmune, TB
45
Symptoms of addison's disease
Hyperpigmentation, fatigue, weakness, anorexia, weight loss
46
What is an addisonian crisis
Failure to respond to stress | Low BP, low glucose, low Na, high K+
47
Diagnosis of addison's disease
Low 9am cortisol High ACTH Short synacthen test (Give ACTH and see if cortisol rises)
48
Management of addison's disease
Replace steroids with hydrocortisone, flurocortisone
49
How do treat an addisonian's crisis
IV fluid resuscitation, IM hydrocortisone
50
What occurs in a 21-Hydroxylase mutation
ACTH rises hyperplastic adrenal glands and so androgen increases (cannot make aldosterone or cortisol as need 21H) - Congenital adrenal hyperplasia
51
Congenital adrenal hyperplasia
Salt losing Adrenal insufficiency Virilisation Adrenal hyperplasia
52
What are catecholamines
Amines made from tyrosine | E.g Dopamine, adrenaline, noradrenaline
53
What converts adrenaline to noradrenaline
PNMT via cortisol Adrenaline → Metadrenaline and NA → Normetadrenaline via COMT
54
Where are chromaffin cells
``` In Adrenal medulla Para-aortic sympathetic chain Organ of zuckerkandl Wall of urinary bladder neck and mediastinal sympathetic chain ```
55
Phaechromocytoma
Chromaffin cell tumour arising from within the adrenal medulla
56
Paraganglioma
Chromaffin cell,, Extra-adrenal tumour
57
both Phaechromocytoma and Paraganglioma
PPGL
58
Input to adrenal medulla
Sympathetic nerves
59
What is released in hypoglycaemic stress
Adrenaline
60
What is released in hypovolemic stress
Noradrenaline
61
A1 adrenoreceptor
vascular and smooth muscle contraction
62
A2 adrenoreceptor
presynaptic, inhibitory to noradrenaline release - suppresses BP
63
B1 adrenoreceptor
positive inotropic and chronotropic in the heart; increased renin; lipolysis
64
B2 adrenoreceptor
bronchial, vascular, uterine smooth muscle relaxation; glycogenolysis
65
B3 adrenoreceptor
Lipolysis, energy expenditure, eg at brown fat tissue
66
D1 adrenoreceptor
cerebral, renal, mesenteric, coronary vasculature dilatation
67
D2 adrenoreceptor
presynaptic inhibition of noradrenaline and prolactin release
68
Catecholamine excess
Impending doom, hypertension, tremor, nausea, vomiting, weight loss, fatigue, dyspnea, headache, fatigue
69
PPGL Case detection
Hyperadrenergic spells, resistant hypertension, familial syndrome

MET2 (28 decks)

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