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MEH 2023 > Session 12 ILOs - The Adrenal glands, RAAS and Adrenal disorders > Flashcards

Session 12 ILOs - The Adrenal glands, RAAS and Adrenal disorders Flashcards

1
Q

Describe the anatomical division of the adrenal gland in terms of the different layers of the cortex and the relationship between the cortex and medulla

To ask:
Is the androgens the main hormone produced by the zona reticularis?

What are androgens - what is the relationship between androgens, oestrogen and testosterone?

A
  • Capsule protects the adrenal glands
  • Cortex is the layer above the medulla but beneath the capsule
  • Cortex - contains 3 layers, each producing different hormones (GFR (Glomerular filtration rate), Salt, sugar, sex)

Zona Glomerulosa - produces mineralocorticoids e.g. aldosterone
Zona Fasiculata - produces glucocorticoids e.g. cortisol
Zona Reticularis - produces glucocorticoids + small amounts of androgens (sex hormones which can be converted to oestrogen and testosterone in peripheral tissues) androgens - e.g testerone and oestrogen

Medulla - contains chromaffin cells
Produces Adrenaline (80%) and Noradrenaline (20%)

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2
Q

Describe the difference in origin tissues of different parts of the adrenal gland

A

Different areas of the adrenal glands arise from different tissues:
Cortex = mesoderm origin
Medulla = neural crest cell origin which subsequently migrate into the developing cortex

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3
Q

Name the hormones produced by the different layers of the adrenal cortex

A

Cortex:

Zona Glomerulosa - mineralocorticoids e.g. aldosterone

Zona Fasciculata - glucocorticoid e.g. cortisol

Zona Reticularis - produces glucocorticoids + small amounts of androgens (sex hormones which can be converted to oestrogen and testosterone in peripheral tissues)

Medulla (not part of the adrenal cortex)
Adrenaline (80%) - fight or flight response
Noradrenaline (20%) - fight or flight response

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4
Q

What are the functions of mineralocorticoids like aldosterone?

A

Zona Glomerulosa - mineralocorticoids e.g. aldosterone
- Central role in regulation of plasma Na+, K+ and arterial blood pressure
- Promotes expression of Na+/K+ pump increasing reabsorption of sodium and water back into the blood
- This influences water retention, blood volume & therefore blood pressure
- Central component of renin-angiotensin-aldosterone system (RAAS)

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5
Q

What are the functions of glucocorticoids like cortisol?

A

Zona Fasciculata - glucocorticoid e.g. cortisol
- Exerts it’s actions by Regulating gene transcription
- Has negative feedback to the hypothalamus to inhibit CRH and ACTH release
- Many actions but main =
- Increased proteolysis in muscle
- Increased lipolysis in fat
- Increased gluconeogenesis in liver
- Anti-inflammatory effects
- Depression of immune response
- Resistance to stress

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6
Q

What are the functions of androgens?

A

Zona Reticularis - androgens
- Promote axillary and pubic hair growth in both sexes
- In males, DHEA converted to testosterone in testes (after puberty this is insignificant since testes release far more testosterone themselves)
- In females, promote libido and are converted to oestrogens by
other tissues. After menopause this is only source of oestrogens.

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7
Q

Give 2 examples of androgens

A
  • (DHEA) and androstenedione are types of androgens
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8
Q

What are the functions of adrenaline, produced from the medulla?

A

Medulla
Adrenaline (80%) - fight or flight response
Noradrenaline (20%) - fight or flight response

F or F: (6)
- Increased HR
- Increased contractility
- Increased bronchodilation
- Increased vasodilation (mucles)
- Increased vasoconstriction (skin and GI tract, so it can go to muscles)
- Increased glycolysis in muscles

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9
Q

Describe in general terms the structure and functions of the steroid hormones

And give 5 examples of steroid hormones

A
  • All made from cholesterol in adrenal glands or gonads
  • All lipid soluble
    Bind to receptors of the nuclear receptor family to modulate gene transcription
    • Glucocorticoids
    • Mineralocorticoids
    • Androgens
    • Oestrogens
    • Progestins
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10
Q

What are corticosteroids?

Name the 2 kinds

A
  • Corticosteroids are a class of steroid hormones
  • Produced in the adrenal cortex or made synthetically. There are two kinds: glucocorticoids and mineralocorticoids
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11
Q

Explain how the steroid hormones affect their target tissues (check discussion board)

Explain how corticosteroids act

A
  • Corticosteroids diffuse across plasma membrane
  • Bind to glucocorticoid receptors which causes dissociation of chaperone proteins
  • Receptor/ligand complex then translocates to the nucleus
  • Dimerisation with other receptors can occur
  • Receptors bind to glucocorticoid response elements or other transcription factors
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12
Q

Explain how cortisol secretion is controlled by ACTH and CRH

A
  • Cortisol is controlled by negative feedback of the hypothalamic pituitary adrenal axis
  • Low ATCH or CRH would decrease cortisol production whereas increased ATCH or CRH would increase cortisol production
  • However, high cortisol would inhibit ATCH or CRH production therefore lowering cortisol levels again
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13
Q

Explain how ACTH can lead to increased pigmentation in certain areas of the body

A
  • Lower levels of ACTH will decrease the level of cortisol
  • Decreased cortisol means that there is decreased negative feedback on the anterior pituitary
  • So we need to synthesise more acth
  • ACTH is made from POMC, so more is POMC required to synthesise ACTH
  • However POMC also makes MSH (melanin stimulating hormone) which increases melanin production and therefore hyperpigmentation
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14
Q

Describe the main actions of cortisol

A
  • Exerts it’s actions by Regulating gene transcription
  • Negative feedback to the hypothalamus to inhibit CRH and ATCH release
  • Increases protein breakdown
  • Increased lipolysis in fat
  • Gluconeogensis in liver
  • Anti-inflammatory effect
  • Immune response depression
  • Resistance to stress
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15
Q

Describe in general terms the structure and functions of adrenaline

A

Adrenaline is formed from Tyrosine

Tyrosine -> Levodopa -> Dopamine -> Noradrenaline -> Adrenaline

N-methyltransferase is required to convert Noradrenaline to Adrenaline

Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response to cause:
SEE IMAGE

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16
Q

Explain how adrenaline exerts its effects on cells

A

Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response

GCPR’s:
G protein : QISS
adrenoreceptor : (a1, a2, b1, b2)

17
Q

Describe the components and overall function of the renin angiotensin aldosterone system

A
  • The RAAS gets activated when BP or BV drops, so it aims to increase them

Renin is released from granular cells in the juxtaglomerulus apparatus - trigged by:
- Reduced NaCl delivery to distal convoluted tubule
- Reduced perfusion pressure in kidneys
- Sympathetic stimulation of JGA - juxtaglomerulus apparatus
(Indicating low BP)

Renin accelerates the conversion of angiotensinogen to angiotensin I and then ACE - angiotensin converting enzyme - converts angiotensin I to angiotensin II

Angiotensin II acts on angiotensin receptor 1 and 2 (mainly on AT1 receptors) to cause effects at 5 different sites :

1) Arterioles - vasoconstriction
2) Kidneys - Stimulates sodium reabsorption at kidney
3) Sympathetic nervous system - increased release of noradrenaline
4)Hypothalamus - increases thirst sensation to increase ADH release
5) Adrenal cortex - stimulates release of Aldosterone

Aldosterone:

  • Central role in regulation of plasma Na+, K+ and arterial blood pressure
  • Promotes expression of Na+/K+ pump increasing reabsorption of sodium and water back into the blood
  • This influences water retention, blood volume & therefore blood pressure (increased bv and bp)
18
Q

Explain the effects of over-secretion and under-secretion of cortisol

A

Over-secretion of cortisol = Addison’s disease (7)
- Weakness
- tiredness
- weight loss
- hypoglycaemia
- increased skin pigmentation
- Postural hypotension
- Annorexia

Under-secretion of cortisol = Cushing’s syndrome
- Cushingoid features ie: (6)

  • buffalo hump
  • purple striae
  • abdominal obesity
  • moon-shaped face
  • Weight gain
  • Hypertension
  • Thin,weak arms and legs
19
Q

Describe tests of adrenal cortical function

A
  • Measurement of plasma cortisol
  • ACTH levels
  • 24hr urinary excretion of cortisol and its breakdown products (these 3 are important in investigating suspected adrenocortical disease)
  • Dynamic function tests may be used in the differential diagnosis of adrenocortical disease:
  • Dexamethasone suppression tests
  • ACTH stimulation tests
  • Dexamethasone (potent synthetic steroid) that (when given orally) normally suppresses secretion of ACTH and thus cortisol
  • Low dose Dexamethasone initially to see whether there is any suppression of cortisol at all (to generally confirm Cushing’s syndrome)
  • High dose Dexamethasone if there is no suppression on low dose
  • Levels of ACTH and cortisol can reveal whether there is Cushing’s disease (caused by a benign pituitary adenoma that secretes ACTH) adrenal Cushing’s (caused by an adrenal tumour producing excess cortisol) or non-pituitary-adrenal tumours producing ACTH and/or CRH (e.g. small cell lung cancer)
20
Q

Explain how cortisol can have weak mineralocorticoid and androgen effects

A

At high concentrations, cortisol can have weak mineralocorticoid and androgen effects

  • The actions of cortisol on target tissues are mediated by binding to receptors in the cytoplasm/nucleus
  • All steroid hormone receptors have similar basic structure with hormone and DNA binding domains
  • The hormone binding domains of the mineralocorticoid and androgen receptors have over 60% sequence homology with the hormone-binding domain of the glucocorticoid receptor
  • Thus, cortisol can bind to these receptors to a limited extent causing their partial activation
21
Q
A
22
Q

Which adrenal hormone is the most serious to be deficient in? (out of mineralocorticoid, cortisol and androgen)

A

Cortisol

MEH 2023 (8 decks)

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