The Adrenal Gland Flashcards

1
Q

Where are the adrenal glands found?

A

Superior pole of the kidney in the retroperitoneal space - each weighing 4g

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2
Q

What does the adrenal gland consist of?

A

Two separate endocrine glands:
• Adrenal medulla
• Adrenal cortex

Both play a role in body’s response to stress

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3
Q

What is the adrenal medulla and its function?

A

It is a modified sympathetic ganglion derived from neural crest tissue.

Secretes catecholamines:
• Mainly epinephrine (adrenaline)
• Norepinephrine
• Dopamine

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4
Q

What is the adrenal cortex and its function?

A

True endocrine gland derived from mesoderm and secretes three classes of steroid hormones:
• Mineralocorticoids i.e. aldosterone
• Glucocorticoids i.e. cortisol
• Sex steroids i.e. testosterone

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5
Q

What is the function of mineralocorticoids (i.e. aldosterone)?

A

Regulation of Na and K

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6
Q

What is the function of glucocorticoids (i.e. cortisol)?

A

Maintaining plasma glucose

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7
Q

Describe the structure of the adrenal gland

A
  • Cortex on the outside arranged in three concentric zones which produce different hormones
  • Medulla on the inside
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8
Q

What are the three concentric zones of the cortex?

A

Outside in:
• Zona glomerulosa –> Aldosterone
• Zona fasciculata –> Glucocorticoids
• Zona reticularis –> Sex hormones

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9
Q

Why do different layers of the adrenal cortex produce different hormones?

A

All steroid hormones are derived from cholesterol, but different enzymes are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona glomerulosa

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10
Q

What hormone does the zona glomerulosa produce?

A

Aldosterone

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11
Q

What hormone does the zona fasciculata produce?

A

Glucocorticoids

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12
Q

What hormone does the zona reticularis produce?

A

Sex hormone

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13
Q

What is the intermediate hormone formed in the ZG when producing aldosterone?

A

Progesterone (+ 21-hydroxylase) –> corticosterone –> aldosterone

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14
Q

What enzyme catalyses the reaction that forms cortisol in the ZF?

A

21-hydroxylase

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15
Q

What is the precursor of estrone and what enzyme catalyses it’s conversion in the ZR?

A

Androstenedione (from progesterone) (+aromatase) –> estrone

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16
Q

What is the precursor of estradiol and what enzyme catalyses it’s conversion in the ZR?

A

Testosterone (from androstenedione) (+aromatase) –> estradiol

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17
Q

What does dihydrotestosterone (DHT) form from?

A

Testosterone

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18
Q

What can DHEA form?

A

Androstenedione (in the ZR) which will form sex hormones

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19
Q

Name a condition caused by defects in 21-hydroxylase?

A

Congenital adrenal hyperplasia

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20
Q

Describe congenital adrenal hyperplasia

A

Deficiency of aldosterone and cortisol and associated disruption of salt and glucose balance.

Androgen biosynthesis is unaffected so accumulating steroid precursors are channelled into excessive adrenal androgen production.

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21
Q

Why is malformed and ambiguous genitalia a clinical features of congenital adrenal hyperplasia?

A

Due to excess production of androgen, as no progesterone is catalysed by 21-hydroxylase.

This causes excess oestrogen, progesterone and testosterone

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22
Q

Name the steps in the hypothalamic-pituitary-adrenal pathway

A

Hypothalamus

  • > CRH
  • > Anterior pituitary
  • > ACTH (short loops neg. feedback on CRH)
  • > Adrenal cortex
  • > Cortisol (short NF on ACTH and long NF on CRH)
  • > Target tissue for response
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23
Q

Why does a deficit in 21-hydroxylase result in adrenal hyperplasia?

A
  1. Lack of 21-hydroxylase inhibits synthesis of cortisol.
  2. This removes the negative feedback on ACTH and CRH release.
  3. Increased ACTH secretion is responsible for enlargement of adrenal glands.
  4. Negative feedback of ACTH on CRH synthesis remains.
  5. ACTH increase –> stimulation of adrenal gland –> hypertrophy
  6. Babies become very ill with a few days of birth
24
Q

What is cortisol?

A

It is a glucocorticoid hormone (influences glucose metabolism).

~95% of plasma cortisol is bound to a carrier protein, cortisol binding globulin (CBG).

25
Q

How does cortisol bind and what are the effects?

A

All nucleated cells have cytoplasmic glucocorticoid receptors.

The hormone receptor complex migrates to the nucleus, binding to DNA via a hormone-response element to alter gene expression, transcription and translation.

26
Q

Describe the pattern of cortisoland ACTH release

A

Marked circadian rhythm:
• Peak is 6-9am
• Cortisol exists in plasma longer than ACTH as it is protected against degradtion as it is bound to a carrier protein and so half life is longer
• Fluctuations during day due to effects of other stimuli related to stress -> hyperglycaemia or the threat of it so cortisol release to prevent

27
Q

Why is cortisol essential for life?

A

Cannot deal with stress, particularly in terms of maintaining blood glucose levels.

As a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia. It has a permissive action on glucagon, which is vital as glucagon alone is inadequate in responding to a hypoglycaemic challenge.

28
Q

What are four actions of cortisol on glucose metabolism (glucocorticoid actions)?

A
  1. Gluconeogenesis
  2. Proteolysis
  3. Lipolysis
  4. Decreases insulin sensitivity of muscles and adipose tissue

Excess cortisol in diabetogenic (diabetes-like effects)

29
Q

How is cortisol involved in gluconeogenesis?

A

Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle (other three actions).

30
Q

How is cortisol involved in proteolysis?

A

Cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver

31
Q

How is cortisol involved in lipolysis?

A

Cortisol stimulates lipolysis in adipose tissue which increases [FFA]plasma creating an alternative fuel supply that allows [BG] to be protected while also creating a substrate (glycerol) for gluconeogenesis.

32
Q

What are four non-glucocorticoid actions of cortisol?

A
  1. Negative effect on Ca balance
  2. Impairment of mood and cognition
  3. Permissive effects on norepinephrine
  4. Suppression of the Immune System
33
Q

How does cortisol have a negative effects on Ca balance?

A

Decreases absorption from gut, increases excretion at kidney resulting in net Ca loss.

Also increase bone resorption –> osteoporosis.

34
Q

How is cortisol involved in the impairment of mood and cognition?

A

Depression and impaired cognitive function are strongly associated with hypercortisolaemia.

35
Q

Describe the permissive effects of cortisol on norepinephrine

A

Particularly in vascular smooth muscle (alpha-receptor effect = vasoconstrictive). Increasing BP.

  • Cushings Disease (hypercortisolaemia) is strongly associated with hypertension.
  • Likewise, low levels of cortisol are associated with hypotension.
36
Q

How does cortisol lead to suppression of the immune system?

A

Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response.

Latter effect can be useful clinically as an anti-inflammatory e.g. asthma/ulcerative colitis/organ transplant.

37
Q

Why does glucocorticoid therapy lead to muscle wastage?

A

Cortisol effect of protein catabolism in muscle and lipolysis in adipose tissue.

Loss of percutaneous fat stores gives appearance of “thinning skin” making it more fragile.

38
Q

What are the side effects of glucocorticoid therapy?

A
  • Increased severity and frequency of infection

* Muscle wastage

39
Q

What is aldosterone?

A

It is a mineralocorticoid, which acts on the distal tubule of the kidney to determine the levels of minerals reabsorbed/excreted.

40
Q

What is the function of aldosterone?

A

It increases the reabsorption of Na+ ions and promotes the excretion of K+ ions.

41
Q

What stimulates aldosterone release?

A

A complex reflex pathway originating in the kidney, the renin-angiotensin-aldosterone system (RAAS).

42
Q

How does aldosterone affect blood pressure?

A

Increased aldosterone release stimulates Na+ (and H2O) retention in plasma and K+ depletion, resulting increased blood volume and increased blood pressure.

Decreased aldosterone leads to Na+ (and H2O) loss and increase [K+]plasma, resulting in diminished blood volume and decreased blood pressure.

43
Q

What conditions are caused by hypersecretion of cortisol?

A
  • Cushing’s Syndrome/Disease

* Iatrogenic - too much administered therapeutically

44
Q

Describe how different causes of hypersecretion of cortisol can cause either Cushing’s Syndrome or Disease

A

Commonly due to a tumour:
• In adrenal cortext (1st degree hypercorticolism) –> Cushing’s Syndrome
• In pituitary gland (2nd degree hypercorticolism) –> Cushing’s Disease (most common, pit. tumour causing excess ACTH -> excess cortisol)

45
Q

What conditions are caused by hyposecretion of cortisol?

A

Addison’s disease
• Hyposecretion of all adrenal steroid hormones
• Due to autoimmune destruction of adrenal cortex

46
Q

What are the characteristic features of Cushing’s Disease?

A
  • Fat deposits in the base of neck, top of back, trunk and around face (reason unknown)
  • Muscle wastage of limbs due to protein catabolic effect of cortisol
47
Q

What is CRH?

A

Corticotropin-releasing hormone

48
Q

What is the relationship between CRH and ACTH?

A

Both promoted by stress.

This is exagerrated by stress causing people to turn to alcohol.

Alcohol, caffeine and lack of sleep all “disinhibit” the Hypothalamo-Pituitary-Adrenal Axis (HPA). Alcohol in particular depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH.

Subsequent elevation of cortisol levels effectively turn down the immune system, increasing vulnerability to infection.

49
Q

Describe the adrenal medualla

A

Modified sympathetic ganglion, not true endocrine tissue. Similar to posterior pituitary in having neuroendocrine role.

Preganglionic sympathetic fibres from the hypothalamus terminate on specialised postganglionic cells in the adrenal medulla. These postganglionic fibres do not have axons – instead they release their neurohormones (adrenaline) directly into the blood.

50
Q

What is pheochromocytoma?

A

Rare neuroendocrine tumour, found in adrenal medulla which results in excess catecholamines: Increase HR -> increase CO -> increase BP

Diabetogenic due to adrenergic effect on glucose metabolism.

Responds well to surgery.

51
Q

What are the effects of CRH, ACTH and cortisol with pathology in the hypothalmus?

A
  • CRH high
  • ACTH high
  • Cortisol high
52
Q

What are the effects of CRH, ACTH and cortisol with pathology in the anterior pituitary?

A
  • CRH low
  • ACTH high
  • Cortisol high

Increase in ACTH will inhibit CRH through short loop neg. feedback

53
Q

What are the effects of CRH, ACTH and cortisol with pathology in the adrenal cortex?

A
  • CRH low
  • ACTH low
  • Cortisol high

Increase in cortisol inhibits ACTH and CRH

54
Q

What needs to be considered when withdrawaing from chronic glucocorticoid treatment?

A

Care is required due to enhanced negative feedback effects of exogenous cortisol.

55
Q

Why can’t you withdraw immediately from chronic glucocorticoid treatment?

A

Additional, therapeutic cortisol enhances the negative feedback on hypothalamus and pituitary reducing release of CRH and ACTH.

Loss of trophic action of ACTH on adrenal gland with immediate withdrawal causes atrophy of gland. Risk of adrenal insufficiency if withdrawal is too fast.

56
Q

What would the effect be with adrenal gland atrophy if withdrawal from chronic glucocorticoid treatment is too fast?

A

Hyperglycaemia