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Metabolism CC > Adrenals > Flashcards

Adrenals Flashcards

1
Q

3 cortical zones

A 
Zona glomerulosa (outer)
Zona fasciculata
Zona reticularis (facing medulla)
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2
Q

Right gland shape

A

Pyramidal

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3
Q

Left gland shape

A

Crescent

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4
Q

Human adrenal gland location

A

Anterior and superior to upper part of kidney

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5
Q

What encloses the medulla

A

Myofibroblasts

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6
Q

Where do veins and lymphatic vessels leave

A

Hilum

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7
Q

Where do arteries and nerves enter the gland

A

Multiple sites

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8
Q

Vessels entering the gland form a…

A

Subcapsular capillary plexus that gives rise to fenestrated sinusoids
–> pass through gland to reach further plexus in ZR

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9
Q

What allows efficient delivery of hormones to bloodstream

A

Most cells in adrenal gland one or two cells away from vascular endothelial cell

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10
Q

Zona Glomerulosa

A

Small, narrow, polyhedral cells in round clusters
Deep staining nuclei + basophilic cytoplasm
Abundant smooth ER
Mitochondria have lamelliform (shelf-like) cristae
15% of cortex
Aldosterone production

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11
Q

Zona Fasciculata

A

Cells larger than ZG
Clear cells- paler staining properties
Laid in columns 2 cells wide, parallel to fenestrated sinusoids
Mitochondrial cristae tubulovesicular in shape
Glucocorticoid- cortisol secretion

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12
Q

Zona Reticularis

A

Smaller, compact cells
Numerous smooth ER + multiple lysosomes with brown lipofuscin pigment
Produces glucocorticoid + secreted adrenal androgens DHEA and DHEAS

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13
Q

What doe ZG secrete

A

Mineralocorticoid- Aldosterone

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14
Q

What does ZF secrete

A

Glucocorticoid- Cortisol

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15
Q

What does ZR secrete

A

Glucocorticoid + adrenal androgens DHEA and DHEAS

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16
Q

Medulla

A

Chromaffin cells
Large, large nuclei + fine cytoplasmic granules which stain brown
Catecholamine hormones packed within granules- released from symp nerve terminals stimulation
80%- adrenaline
20%- noradrenaline

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17
Q

Medulla secretes

A

80% cells adrenaline

20% cells noradrenaline

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18
Q

Steroid production

A

Cholesterol uptake
Cholesterol –> inner mitochondrial membrane
Converted to pregnenolone by cytochrome P450

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19
Q

Aldosterone release stimulated by

A

Secreted by ZG

ZG cells respond to ACTH, but angiotensin II + K extracellular conc increase are main regulators

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20
Q

Aldosterone release inhibition

A

Somatostatin
Heparin
ANP
Dopamine

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21
Q

Binding of Ang II to GPCR AT1

A

Activates downstream signalling pathways
Mostly phospholipase C activation –> Ca2+ intracellular increase
Increasing K+ depolarises ZG cell membrane, also leading to Ca2+ influx
In long term, upregulated aldosterone synthase

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22
Q

Aldosterone effects

A 
Mediated by binding to mineralocorticoid receptor in cytosol
Increases retention of sodium and water
Stimulates NaK ATPase
Inserts additional ENaC
Stimulates H+ ATPase
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23
Q

Mineralocorticoid receptor (MR) affinity

A

Equal affinity to both cortisol and aldosterone

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24
Q

Cortisol clearance

A

Cortisol inactivated into cortisone by action of 11BetaHSD-2 in kidney

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25
Aldosterone binding to MR
Induces retention of Na+ by upregulating epithelial Na+ channels (ENaC) in distal tubules
26
Hypertension caused by hyperaldosteronism
Direct action of aldosterone on vasculature and CNS Aldosterone can promote inflammation and oxidative stress Oxidative stress upregulates MR expression in cardiac cells -->induces cardiac remodelling + fibrosis Aldosterone causes impaired insulin signalling --> induces swelling + stiffening of endothelial cells + counters ability to trigger vasodilation
27
Primary hyperaldosteronism causes
Conn's syndrome Aldosterone-producing adenoma Bilateral adrenal hyperplasia
28
Conn's syndrome
Hypertension Suppressed plasma renin activity Increased aldosterone production
29
Primary hyperaldosteronism diagnosis
``` Aldosterone:Renin ratio Saline suppression test CT adrenal Adrenal venous sampling Metomidate PET ```
30
Primary hyperaldosteronism treatment
MR antagonists- spironolactone, eplerenone | Unilateral adrenalectomy- proven single aldosterone-secretion adenoma
31
Liddle Syndrome
Mutation that inserts additional ENaC --> more Na+ taken from filtrate Stimulates Na+/K+ ATPase --> 3Na+ reabsorbed into bloodstream in exchange for 2K+, which is excreted
32
Liddle Syndrome effects
Hypertension Hypokalaemia Metabolic acidosis
33
Familial Aldosteronism
Autosomal dominant ACTH dependent activation of aldosterone synthase Can be reversed by treatment with glucocorticoid to inhibit ACTH from pituitary gland
34
Familial Aldosteronism effects
Early onset, severe, refractory hypertension Early onset haemorrhagic stroke No hypokalaemia
35
Syndrome of Mineralocorticoid Excess
Cortisol inactivated into cortisone by 11BetaHSD2 in kidney so aldosterone allowed to bind to MR This doesn't happen in conditions of Cortisol excess or where enzyme has been affected --> eating excess liquorice can inactivate 11BetaHSD2
36
Mineralocorticoid excess effects
Low K+ Metabolic alkalosis Low plasma renin Low aldosterone
37
ACTH
``` Produced by anterior pituitary Binds to MC2R (melanocortin-2 receptor) Increases cholesterol import into cell Increases cholesterol trafficking into mitochondria Increases adrenal blood flow ZF growth ```
38
ACTH and Cortisol secretion
Circadian rhythm Begins at 4am, peaks at 7am, Daily ACTH higher in males Stress increases amplitude
39
Glucocorticoid production
Under HPA axis control Activation of parvocellular neurones of paraventricular nucleus synthesise + secrete CRH and AVP into hypophyseal circulation CRH binding to CRH receptor leads to ACTH release in systemic circulation ACTH binds to MC2R in ZF Activates cAMP downstream signalling pathways Adrenal blood flow increases + ZF layer hypertrophies ZF secretes glucocorticoid- CORTISOL
40
Glucocorticoid effect
Modify glucose metabolism | Stimulate gluconeogenesis + antagonise insulin
41
Glucocorticoids + Stress starvation
Causes Tissue breakdown for fuel
42
Glucocorticoids + stress infection
Causes immunosuppression
43
Glucocorticoids + Stress hypotension
Increases BP
44
Cortisol in CV system
Increases transcription receptors for angiotensin II, epinephrine and norepinephrine --> maintain BP
45
Cushing's syndrome Signs
``` Moon face Buffalo hump Easy bruising Purple Striae- obesity Ulcers High BP Osteoporosis + muscle weakness ```
46
Cushings syndrome- what is it
Excess cortisol
47
Cushings syndrome causes
``` Iatrogenic Corticotroph adenoma of pituitary Ectopic ACTH secreting neuroendocrine tumour Cortisol secreting adrenal adenoma Bilateral adrenal hyperplasia ```
48
Cushings syndrome Diagnosis
Overnight dexamethasone suppression test 24 hour urine free cortisol Cortisol day curve plus midnight sleeping cortisol
49
Cushings Imaging
MRI Pituitary | CT adrenals
50
Cushings treatment- pituitary
Transsphenoidal surgery | External beam radiotherapy
51
Cushings treatment- adrenal
Adrenalectomy | Metyrapone
52
Addisons disease
Primary adrenal failure- autoimmune, tuberculosis | Low cortisol
53
Addisons symptoms
Faitgue, weakness, myalgia Anorexia, weight loss Hyperpigmentation
54
Addisonian crisis
Failure to respond to stress Low BP Low Glucose Low Na, High K
55
Addisons diagnosis
Low 9am cortisol High ACTH Short Synacthen test
56
Addisons management
Replacement steroid- hydrocortisone, fludrocortisone | Addisonian crisis- IV fluid resuscitation, IM hydrocortisone
57
21 Hydroxylase deficiency
can leas to congenital adrenal hyperplasia Salt losing Adrenal insufficiency
58
Catecholamines
``` Adrenaline Noradrenaline Dopamine Release stimulated by ACh release from preganglionic Symp Nerves BUT basal secretion without neural imput ```
59
Chromaffin cells
Adrenal medulla Wall of urinary bladder Neck + mediastinal symp. chain
60
Phaeochromocytoma
Chromaffin cell tumour | Arising from within adrenal medulla
61
Paraganglioma
Chromaffin cell tumours | Extra-adrenal tumours
62
Catecholamine release
Haemorrhage- noradrenaline | Hypoglycaemia- adrenaline
63
Fight or flight response
60 fold increase in catecholamine secretion
64
Alpha 1 adrenoreceptor
Vascular and smooth muscle contraction
65
Alpha 2 adrenoreceptor
Presynaptic Inhibitory to noradrenaline release Suppresses BP
66
Beta 1 adrenoreceptor
Positive inotropic and chronotropic in the heart Increased renin Lipolysis
67
Beta 2 adrenoreceptor
Bronchial, vascular, uterine smooth muscle relaxation | Glycogenolysis
68
Beta 3 adrenoreceptor
Lipolysis Energy expenditure e.g. at brown fat tissue
69
D1 adrenoreceptor
Cerebral, renal, mesenteric, coronary vasculature dilatation
70
D2 adrenoreceptor
Presynaptic inhibition of noradrenaline and prolactin release
71
Catecholamine excess
``` Dyspnea Headache Hypertension Palpitation Nausea Tremor Hyperglycaemia ```
72
PPGL tumour treatment
Pre-operative alpha and beta blockade - need both | Avoid opiates
73
PPGL Tumour treatment- beta blockers
Don't treat with only this, as will cause vasoconstriction in an already hypertensive state

Metabolism CC (29 decks)

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