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LCRS > Endocrinology 8 - Adrenals and their Hormones > Flashcards

Endocrinology 8 - Adrenals and their Hormones Flashcards

1
Q

Where are the adrenal glands located?

A

Embedded on the superior pole of each of the two kidneys.

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2
Q

What are the different parts of the adrenal gland?

A
  1. Adrenal Medulla - the centre of the gland.

2. The outer part is the cortex and has 3 zones - zona glomerulosa, zona fasciculata, zona reticularis.

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3
Q

What is the Adrenal medulla made of and what does it produce?

A
  1. It is made of chromaffin cells - post ganglionic nerve fibers in specialized form.
  2. Produces Catecholamines (Adrenaline 80%, noradrenaline 20% and dopamine - small amounts).
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4
Q

What does the cortex produce?

A

Corticosteroids

  1. Mineralocorticoids - Aldosterone
  2. Glucocorticoids - Cortisol.
  3. Sex steroids - mall amounts of androgens and oestrogens.
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5
Q

Which part of the cortex does Aldosterone come from?

A

The zona glomerulosa.

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6
Q

Which part of the cortex does Cortisol and sex steroids come from?

A

The two inner zones of the cortex (zona reticularis and zona fasciculata).

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7
Q

Describe Cortisol synthesis

A
  1. Cholesterol => Pregnenolone => 17-a-hydroxypregnenolone => 17-a-hydroxyprogesterone => 11-b-deoxycortisol => Cortisol
  2. Cholesterol => Pregnenolone => Progesterone => 17-a-hydroxyprogesterone => 11-b-deoxycortisol => Cortisol.
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8
Q

Describe Aldosterone synthesis

A

Cholesterol => Pregnenolone => Progesterone => 11-deoxycorticosterone => corticosterone => Aldosterone

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9
Q

What is the difference in the synthesis pathway between aldosterone and cortisol?

A

Cortisol has the P450c17 enzyme but aldosterone does not.

Aldosterone has the aldoesterone synthase enzyme but cortisol does not.

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10
Q

How is cortisol transported in the blood?

A
  1. 80% bound to corticosteroid binding globulin (CBG).
  2. 10% bound to albumin.
  3. 10% free.
    Cortisol is much more selective to CBG.
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11
Q

How is Aldosterone transported in the blood?

A
  1. 40% free.
  2. 15% bound to CBG.
  3. 45% bound to albumin.
    Aldosterone is much less selective compared to cortisol, hence there is more free aldosterone.
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12
Q

Is there a higher concentration of cortisol or aldosterone in the blood?

A

Cortisol, by a 1000 fold.

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13
Q

Do cortisol levels change throughout the day?

A
  1. Yes, it depends on the time of the day.

2. Cortisol is also released in pulses.

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14
Q

Do aldosterone levels change throughout the day?

A
  1. no, your POSITION is more important as aldosterone in involved in control of fluid and balance.
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15
Q

What are the actions of aldosterone? (2)

A
  1. Stimulates Na+ reabsorption in the distal convoluted tubule and cortical collecting duct (important in kidneys and sweat glands).
  2. Stimulates K+ and H+ secretion in the distal convoluted tubule and cortical collecting duct (important for pH regulation of the blood).
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16
Q

What is the mechanism of action of aldosterone?

A
  1. Diffuses into the cell and binds to intracellular receptors.
  2. The complex formed moves into the nucleus and binds to DNA - acts as transcription factor.
  3. Stimulates the synthesis of certain proteins for enzymes or pumps.
  4. Also stimulates action of the Na+ ATPase pump on basolateral membrane.
  5. Stimulates synthesis of Na+ ion channels on apical membrane.
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17
Q

How does aldosterone stimulate the release of vasopressin?

A
  1. Aldosterone stimulates the reabsorption of Na+ into the blood.
  2. This increases the osmolality of the blood.
  3. Increased osmolality of the blood stimulates the release of vasopressin.
18
Q

What is a long term problem you get if you maintain a high extracellular fluid volume?

A

Hypertension.

19
Q

What is the name given to the specialized cells that line the afferent arteriole into the kidneys that are next to the glomerulus?

A

The Juxta-glomerular cells.

20
Q

What is the name given to the specialized cells that line the ascending limb of the loop of Henle? And what do they respond to?

A

Macula Densa. Changes in Na+ concentration.

21
Q

What is the enzyme important for the production of aldosterone? And cells produce this enzyme?

A

Renin. Produced by the juxta-glomerular cells.

22
Q

What are the causes of Renin release? (3)

A
  1. Decreased renal perfusion pressure.
  2. Decreased Na+ load to the top of the loop of Henle.
  3. Increased renal sympathetic activity (JGA has sympathetic innervation.
23
Q

How does Renin stimulate the production of aldosterone?

A
  1. Angiotensinogen (large protein) is released by the liver.
  2. Renin breaks down angiotensinogen into angiotensin I.
  3. ACE converts angiotensin I into angiotensin II.
  4. Angiotensin II stimulates aldosterone production in the zona glomerulus.
24
Q

What are the other effects of angiotensin II

A

Vasoconstriction.

25
Q

What are other factors that affect aldosterone? (3)

A
  1. Corticotrophin - enhances renin-angiotensin system.
  2. Low Na+ concentration in the blood (increased reabsorption of Na+).
  3. High K+ concentration in the blood (increased secretion of K+).
26
Q

What are the metabolic effects of cortisol?

A

OVERALL EFFECT TO INCREASE BLOOD GLUCOSE CONCENTRATION.

  1. Stimulates peripheral protein catabolism.
  2. Hepatic gluconeogenesis.
  3. Lipid metabolism.
  4. Enhances effects of glucagon and catecholamines.
  5. Stimulates glycogenolysis.
  6. Makes tissues less responsive to insulin.
27
Q

What is the syndrome as a result of excessive cortisol production?

A

Cushing’s syndrome - arms and legs really thin because of the loss of muscle.

28
Q

How does cortisol affect memory?

A
  1. Serotonin promotes granule cell division (used to make memories).
  2. Cortisol enhances the sensitivity of serotonin receptors in the hippocampus.
29
Q

What are the effects of supra-physiological amounts of cortisol?

A
  1. Anti-inflammatory action.
  2. Immunosuppressive action.
  3. Anti-allergic action.
30
Q

Which receptor does aldosterone bind to?

A

Almost entirely to the mineralcorticoid receptor (MR).

31
Q

Which 2 receptors does cortisol bind to?

A

Binds equally to both the mineralcorticoid and the glucocorticoid receptor.

32
Q

Why doesn’t cortisol constantly bind to the aldosterone receptors even though it has a concentration 1000 times greater than aldosterone?

A

Because the kidneys produce an enzyme (11-beta-hydroxysteroid dehydrogenase II), which converts cortisol into an inactive form cortisone. This prevents cortisol interfering with aldosterone receptors.

33
Q

Explain the mechanism of cortisol, use annexin 1 as an example.

A

Cortisol binds to intracellular receptors and has a genomic effect. Example is one protein produced called annexin 1.

  1. Annexin 1 has an autocrine effect on cell.
  2. The binding has effect on phospholipase enzyme, which works on phospholipids in the membrane to produce arachidonic acid that is a precurser to prostaglandins.
  3. Therefore cortisol blocks the production of prostaglandins.
34
Q

How is cortisol levels controlled?

A
  1. Corticotrophin controlled by hypothalamic hormones.
  2. Cortisol has negative feedback - direct (pituitary) and indirect (hypothalamus).
  3. ACTH has negative feedback on hypothalamus.
  4. There is a circadian rhythm for cortisol which originates from biological cock, which resides in the suprachiasmatic nucleus.
35
Q

How should blood sampling be arranged for cortisol?

A

Cortisol levels vary with time and therefore blood sampling should be done when cortisol levels are expected to be at its highest or lowest.

36
Q

What is the androgen produced by the adrenal glands?

A

DHEA. It is a very weak androgen and is a precursor for oestrogen. Important to post-menopausal women as a precursor for oestrogen in the absence of ovarian steroids.

37
Q

In what 2 ways is blood passed down to the zones?

A
  1. Most passed through the cells.

2. There are some vessels which go through cortex to get to the medulla.

38
Q

Which part of the ANS is the adrenal medulla associated with?

A

The sympathetic nervous system.

39
Q

Why are steroids not stored?

A

They are lipophilic and can pass easily through membranes.

40
Q

What is Androstenedione?

A
  1. It is a weak androgen androgen produced in the adrenal cortex.
  2. They are made more powerful in the testes.
41
Q

What is the action of vasopressin and where does it act?

A

Increases water reabsorption in the kidney collecting duct.

LCRS (22 decks)

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