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Year 2 - T2 Theme 1 > L6 - Adrenal cortex - hormones, physiology > Flashcards

L6 - Adrenal cortex - hormones, physiology Flashcards

1
Q

Location of adrenal glands

A
  • The adrenal glands lie on top of the kidneys
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2
Q

Division of the adrenal cortex

A
  • Inner adrenal medulla (10%)

- Outer adrenal cortex (90%)

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3
Q

What is the adrenal medulla concerned with

A
  • Stress response
  • Cortex with stress, sodium and glucose homeostasis
  • Unlike the adrenal medulla, a functioning adrenal cortex is essential for life
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4
Q

What does the adrenal cortex synthesise

A
  • Many different hormones of a similar chemical structure (steroid hormones)
  • Derived from cholesterol from the diet or synthesised within the gland itself
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5
Q

Divisions of the adrenal cortex

A
  • Outer zona glomerulosa
  • Middle zona fasciculata
  • Innermost zona reticularis
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6
Q

How are steroid hormones classified

A

Steroid hormones produce a variety of effects, but they are usually classified according to their predominant action, thus the major secretions of the adrenal cortex are the:

glucocorticoids (eg cortisol)
Mineralocorticoids (eg aldosterone)

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7
Q

What is synthesised in the zona glomerulosa

A
  • 18-hydroxylase enzyme hence aldosterone synthesis
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8
Q

What is synthesised in the zona fasiculata and zona reticularis

A
  • 17a-hydroxylase hence 17a-hydroxypregenolone, 17a-hydroxyprogesterone and the hormones derived from them
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9
Q

Where is cortisol synthesised

A
  • Zona fasciculata
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10
Q

Where are androgens synthesised

A
  • Zona reticularis
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11
Q

What are sex hormones (androgens) secreted by the adrenal cortex under normal circumstances

A
  • Under normal circumstances the adrenal cortex secretes small quantities of male sex hormones (androgens) such as dehydroepiandrosterone, androstenedione and testosterone, and the female oestrogens eg oestradiol.
    Only significant in adrenal disorders.
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12
Q

Control of glucocorticoid secretion by HPA

A

Hypothalamus - CRH –> Anterior pituitary gland - ACTH –> Adrenal cortex - cortisol (feedback effect on hypothalamus)

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13
Q

Secretion patterns of ACTH

A
  • Pulsatile
  • Peak in the early morning, at the time of waking
  • Increased secretion at time of prolonged stress
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14
Q

Cortisol secretion pattern vs ACTH secretion pattern

A
  • Cortisol secretion shows the same pattern but the peak and nadir occurs approximately 2 hours later than those of ACTH
  • This pattern is related to sleep - wake patterns: disrupted by shift work and long-haul travel
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15
Q

What percentage of cortisol within the blood is in a free, active form

A

10% of cortisol

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16
Q

Plasma proteins bound to cortisol

A
  • Corticosteroid binding globulin (CBG or transcortin) 75%
  • Albumin 15%
  • The same proteins also transport the other glucocorticoids and progesterone
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17
Q

Link between pregnancy and CBG(corticosteroid-binding globulin)

A
  • Pregnancy is associated with an increase in CBG which results in a compensatory increase in circulating plasma cortisol concentrations
  • The amount of free cortisol remains stable
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18
Q

Where does the metabolism of the adrenal steroids mainly occur

A
  • In the liver where they are glucouronidated to form water soluble forms which are excreted in the urine
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19
Q

How do glucocorticoids produce their effects

A

In common with all other steroid hormones, glucocorticoids produce their effects by an action on intracellular receptors and alterations in gene expression: inevitably results in a delay, in the order of hours or days,

In some cases the effects of cortisol are rapid eg feedback inhibition of ACTH secretion.

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20
Q

What are the most important actions of cortisol at normal physiological concentrations

A

At normal physiological concentrations the most important actions of cortisol are those on carbohydrate metabolism.
Cortisol opposite to insulin, i.e.
• Antagonizes the effects of insulin on cellular uptake of glucose
• Stimulates glycogenolysis
• Stimulates hepatic gluconeogenesis.

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21
Q

Effect of cortisol on lipolysis and mobilisation of fatty acids

A
  • Cortisol stimulates lipolysis and mobilization of fatty acids, partially by potentiating the effects of growth hormone and the catecholamines
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22
Q

Effect of excess cortisol on fat synthesis

A
  • In excessive concentrations cortisol causes fat synthesis and deposition in novel anatomical sites, most notably the face, the trunk and the intrascapular region of the shoulders.
23
Q

Action of cortisol in the liver

A
  • In the liver, cortisol stimulates amino acid uptake leading to enhanced gluconeogenesis
  • In the periphery it inhibits amino acid uptake and protein synthesis, resulting in a net loss of skeletal protein.
24
Q

Effect of excess cortisol on vasoconstrictor responses

A
  • Enhanced vasoconstrictor responses to catecholamines which results in increased blood pressure
25
Q

Psychological effects of glucocorticoids

A
  • Can potentially produce feelings of elation or sedation
  • At times of psychological and physiological stress such as trauma, infection or hypoglycaemia, there is a rapid secretion of ACTH and corticosteroids.
    At these raised concentrations additional effects of these hormones become apparent.
26
Q

How do glucocorticoids affect the body’s defence systems

A
  • They suppress the lymphoid tissue, reduce the antibody production and inhibit the cellular immune system.
  • They stabilize leucocyte membranes and reduce the release of proteolytic enzymes.
  • They inhibit phospholipase A2 and reduce the synthesis of the inflammatory mediators.
27
Q

Why are glucocorticoids important during times of prolonged stress

A

At times of prolonged stress the glucocorticoids maintain the enhanced supply of glucose which may be required for the prolonged response to the stressor but they also suppress of the inflammatory response

28
Q

Inflammatory response at times of injury

A
  • Pain alerts the sufferer to the damage
  • Oedema dilutes any toxic substances that may be present and immobilises and stabilises joints.
  • Infiltration by leucocytes destroys any invading cells whilst antibodies inactivate the foreign proteins.
  • Tissue repair is enhanced by prostaglandins
29
Q

Effect of the adrenocortical stress response on the inflammatory response

A
  • The adrenocortical stress response decreases the inflammatory response
  • It removes the pain and decreases the immobilisation induced by the oedema
  • Steroid-induced sedation also causes a lack of awareness of the severity of the situation
  • The overall effect is that the individual is able to perform despite the presence of the injury or infection
30
Q

What are the physiologically important mineralocorticoids

A
  • Aldosterone

- 11-deoxycorticosterone

31
Q

How does ACTH affect the secretion of aldosterone

A
  • The secretion of aldosterone is relatively uninfluenced by ACTH, although ACTH stimulates the initial conversion of cholesterol to pregnenolone
  • The major controlling factor is the secretion of aldosterone is the renin-angiotensin system
32
Q

What is the secretion of aldosterone directly stimulated by

A
  • Trauma, anxiety, hyperkalaemia and hyponatraemia
33
Q

What is the secretion of aldosterone inhibited by

A
  • atrial natriuretic peptide (ANP)
34
Q

What percentage of aldosterone is protein bound within the circulation

A
  • 50%
35
Q

Effect of aldosterone on ion channel expression in the cell membrane

A
  • Aldosterone has specific intracellular receptors which cause expression of ion channels that transport sodium and potassium ions across the cell membrane
36
Q

Where does aldosterone stimulate the reabsorption of sodium ions

A

Aldosterone stimulates the reabsorption of sodium ions in the distal tubule of the kidney, with some lesser effects in the collecting duct, proximal tubule and ascending loop of Henlé, and in the colon, sweat and salivary glands.

37
Q

What does sodium reabsorption occur in exchange for

A
  • Either potassium or hydrogen ions
38
Q

How does aldosterone influence water reabsorption

A

By controlling reabsorption of sodium ions, aldosterone influences plasma sodium concentration, which in turn influences water reabsorption in the collecting duct via an effect on ADH secretion

39
Q

Pharmacological uses of glucocorticoids

A

Glucocorticoids (eg hydrocortisone = cortisol) are used in replacement therapy and for their immunosuppressive or anti-inflammatory effects in conditions such as arthritis, asthma or allergies, or for the treatment of proliferative conditions such as leukaemia.

40
Q

Pharmacological uses of mineralocorticoids

A

Mineralocorticoids are used only for replacement therapy.
The short plasma half-life of aldosterone renders it unsuitable for mineralocorticoid replacement therapy thus the drug of choice is fludrocortisol.

41
Q

What is the selection of the glucocorticoid dependent on

A

In most cases the selection of the glucocorticoid is dependent upon the pharmacokinetics of the available agents and the predominant effect required.
Most glucocorticoids are orally active but their absorption through the skin varies as does their plasma half-life.

42
Q

Adverse effects associated with the use of glucocorticoids

A

Steroid usage may suppress wound healing and may exacerbate infections due to their immunosuppresant effects.

Long term use in children may cause inhibition of growth, and in adults may result in osteoporosis.

The development of diabetes mellitus and other symptoms of Cushing’s syndrome also often accompanies steroid therapy.

43
Q

Most important adverse effect of glucocorticoid use

A

Suppression of the hypothalamic-pituitary axis.
Chronic administration of exogenous glucocorticoids results in suppression of ACTH secretion leading to atrophy of the adrenal cortex.

44
Q

What happens if steroid therapy is stopped abruptly

A

If steroid therapy is then stopped abruptly, the adrenal cortex is unable to secrete endogenous hormones and the patient suffers an Addisonian crisis, which may be fatal.

This consequence overcome by the gradual reduction of the dose of the exogenous steroid
Other consequences of suppression of the anterior pituitary may include disturbances of sex hormone secretion resulting in symptoms such as menstrual disturbances.

Anti-inflammatory corticosteroids remove the symptoms without affecting the cause of the underlying disorder, which may worsen.

45
Q

What is hydrocortisone (cortisol)

A
  • A natural glucocorticoid secreted by the adrenal cortex
46
Q

How does hydrocortisone act

A
  • It acts via specific intracellular glucocorticoid receptors to influence gene expression
47
Q

When are glucocorticoids used

A
  • Typically used for hormone replacement therapy, as anti-inflammatory agents and immunosuppressants
  • Hydrocortisone is the drug of choice for replacement therapy
48
Q

Oral bioavailability of hydrocortisone

A
  • 60-80%
49
Q

Protein binding of hydrocortisone

A
  • High
50
Q

Metabolism of hydrocortisone

A
  • Hepatic
51
Q

Approximate half-life of hydrocortisone

A
  • Approx 1.5
52
Q

Standard dose of hydrocortisone

A

15-20 mg per day in divided doses

53
Q

Adverse effects of hydrocortisone

A
  • Hyperglycaemia
  • Osteoporosis
  • Cushing’s syndrome

Year 2 - T2 Theme 1 (20 decks)

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