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Year 2 Medicine > Adrenal Cortex - Hormones, Physiology > Flashcards

Adrenal Cortex - Hormones, Physiology Flashcards

1
Q
  • The adrenal glands lie on top of the …
A

kidneys

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2
Q
  • In the US - the adrenal glands are known as
A

suprarenal glands

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3
Q

The adrenal glands are divided into inner adrenal… (10%) and the outer adrenal… (90%)

A
  • inner adrenal medulla (10%) outer adrenal cortex (90%)
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4
Q

The medulla is concerned with what response?

A

stress response

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5
Q

The cortex is concerned with what response?

A

stress, sodium and glucose homeostasis

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6
Q
  • One part of the adrenal gland is required to be functional - this is essential for life
  • what part is this?
A

The adrenal cortex must be functional!

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7
Q
  • The adrenal… synthesises many different hormones of a similar chemical structure (… hormones)
  • Derived from … from the diet or synthesized within the gland itself.
A
  • cortex (steroid hormones)
  • derived from cholesterol from the diet
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8
Q

What group of hormones are shown?

A

Steroid hormones

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9
Q

The adrenal cortex is divided into three distinct layers, what are these?

A
  1. Outer zona glomerulosa
  2. Middle zona fasciculata
  3. Innermost zona reticularis
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10
Q

Cells within the different areas of the adrenal cortex possess different … and therefore synthesise different … hormones

A

Cells within the different areas of the adrenal cortex possess different enzymes and therefore synthesise different adrenocortical hormones

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11
Q

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:

  1. … (e.g. cortisol)
  2. … (e.g. aldosterone)
A
  1. glucocorticoids (e.g. cortisol)
  2. mineralocorticoids (e.g. aldosterone)
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12
Q

Synthetic pathway - adrenal cortex

  • we start with … which feeds in, and is converted to pregnenolone
  • Pregnenolone is then either converted into progesterone (what pathway?) or made into 17a OH Pregnenolone, which then goes into one of two pathways (… pathway or … pathway)
A
  • we start with cholesterol -> converted to pregnenolone -
  • Pregnenolone is then either converted into progesterone (mineralocorticoid pathway) or made into 17a OH Pregnenolone, which then goes into one of two pathways (glucocorticoid pathway or androgen pathway)
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13
Q
  • In the zoma glomerulosa, do we have the enzyme 17a-hydroxylase?
    • what does this mean?
A
  • No - it is not present here hence cortisol and androgens cannot be synthesized in this layer, only aldosterone
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14
Q
  • In the zoma fasciculata and zona reticularis, do we have the enzyme 17a-hydroxylase?
  • what does this mean?
A
  • yes we do - it is present hence 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and the hormones derived from them.
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15
Q

Androgens are synthesized where? (within adrenal cortex)

A

zona reticularis

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16
Q

Cortisol is synthesized where? (within adrenal cortex)

A

zona fasciculata

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17
Q

Aldosterone is synthesized where? (adrenal cortex)

A

zona glomerulosa

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18
Q
  • Under normal circumstances, the adrenal cortex secretes small quantities of male sex hormones (known as what?) such as dehydroepiandrosterone, androstenedione and testosterone, and the female …. e.g oestradiol
  • these are only secreted in significant amounts in adrenal …
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 e.g oestradiol
  • these are only secreted in significant amounts in adrenal disorders
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19
Q

Synthesis, secretion and actions of the mineralocorticoids and the glucocorticoids are controlled …

A

independently

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20
Q

Control of glucocorticoid secretion

  • Hypothalamus releases … releasing hormone
  • works on pituitary gland to release …
  • goes to adrenal cortex and … cortisol production
  • cortisol levels … - negative feedback mechanism - switching … CRH
A
  • Hypothalamus releases Corticotrophin releasing hormone
  • works on pituitary gland to release Adrenocorticotropic hormone (ACTH)
  • goes to adrenal cortex and stimulates cortisol production
  • cortisol levels rise - negative feedback mechanism - switching off CRH
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21
Q
  • The secretion of ACTH is pulsatile, meaning it peaks in the … at the time of … and is at it’s lowest point in …
  • there is increased secretion in times of prolonged …
  • disrupted by shift work and long-haul travel
A
  • The secretion of ACTH is pulsatile, meaning it peaks in the early morning at the time of waking and is at it’s lowest point in the middle of the night
  • there is increased secretion in times of prolonged stress
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22
Q

Cortisol secretion shows the same pattern as secretion of …. but the peak and lowest point occurs approximately how much later than those of …

This pattern is related to sleep - meaning it is disrupted by what?

A
  • ACTH
  • Approx 2 hours later
  • disrupted by shift work and long-haul travel
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23
Q

Transport of glucocorticoids

  • Only 10% of cortisol within the blood is in what form?
  • is this form active or non-active?
  • the remainder is bound to what? (give 2 examples and % found)
A
  • Only 10% of cortisol within the blood is in free form
  • is this form active or non-active? - active
  • the remainder is bound to what? (give 2 examples)
    • plasma proteins - corticosteroid binding globulin (CBG or transcortin, 75%) and albumin (15%)
    • the same proteins also transport the other glucocorticoids and progesterone
24
Q

Pregnancy is associated with an increase in CBG which results in a compensatory increase in circulating plasma … concentrations

A
  • cortisol
  • the amount of free cortisol remains stable
25
Q

Metabolism of the adrenal steroids occurs mainly in the … where they are … to form water soluble forms which are excreted in …

A
  • liver
  • glucuronidated
  • excreted in urine
26
Q

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

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
27
Q

In some cases the effects of cortisol are … e.g. feedback inhibition of ACTH secretion

A

rapid

28
Q

At normal physiological concentrations the most important actions of cortisol are those on … metabolism

Cortisol works in an opposite way to Insulin, i.e. it …

  1. stimulates glycogeno…
  2. stimulates hepatic …
  3. antagonizes the effects of insulin on cellular uptake of …
A
  • carbohydrate metabolism
  • Cortosil works in an opposite way to Insulin, i.e. it …
  1. stimulates glycogenolysis
  2. stimulates hepatic gluconeogenesis
  3. antagonizes the effects of insulin on cellular uptake of glucoser
29
Q

Cortisol also stimulates lipo… and mobilization of …acids, partially by potentiating the effects of growth … and the …

A
  • Cortisol also stimulates lipolysis and mobilization of fatty acids, partially by potentiating the effects of growth hormone and the catecholamines
30
Q

In excessive concentrations cortisol causes fat … and deposition in novel anatomical sites, most notably the … and the intrascapular region of the …

A

In excessive concentrations cortisol causes fat synthesis and deposition in novel anatomical sites, most notably the faceand the intrascapular region of theshoulder

31
Q
  • In the liver, cortisol stimulates amino acid … leading to enhanced …
  • In the periphery, it inhibits amino acid … and protein …, resulting in a net loss of … protein
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
32
Q
  • Glucocorticoids are also able to stimulate … receptors although …-sensitive tissues possess an enzyme, 11B-hydroxysteroid dehydrogenase1, which converts cortisol to inactive …
  • mineralocorticoid actions of glucocorticoids only apparent at … concentrations
A
  • Glucocorticoids are also able to stimulate aldosterone receptors although aldosterone-sensitive tissues possess an enzyme, 11B-hydroxysteroid dehydrogenase1, which converts cortisol to inactive cortisone
  • mineralocorticoid actions of glucocorticoids only apparent at high concentrations
33
Q
  • Another effect of excess cortisol is an enhanced … response to catecholamines which results in … blood pressure
A

Another effect of excess cortisol is an enhanced vasoconstrictor response to catecholamines which results in increased blood pressure

34
Q
  • Glutocorticoids also produce psychological effects with possible feelings of ..ation or ..dation
A

Glutocorticoids also produce psychological effects with possible feelings of elationor sedation

35
Q

At times of psychological and physiological stress (give examples of 3), there is a rapid secretion of … and ….

At these raised concentrations additional effects of these hormones become apparent

A

At times of psychological and physiological stress (infection, trauma, hypoglycaemia) , there is a rapid secretion of ACTH and corticosteroids.

At these raised concentrations additional effects of these hormones become apparent

36
Q

Glucocorticoids affect the body’s defence systems at many level.

They may:

  1. Suppress the … tissue, reduce the … production and inhibit the cellular immune …
  2. They stabilize leucocyte membranes and reduce the release of … enzymes
  3. They inhibit phospholipase A2 and reduce the synthesis of the inflammatory ….
A

They may:

  1. Suppress the lymphoid tissue, reduce the antibody production and inhibit the cellular immune system.
  2. They stabilize leucocyte membranes and reduce the release of proteolytic enzymes
  3. They inhibit phospholipase A2 and reduce the synthesis of the inflammatory mediators
37
Q

There are many effects of glucocorticoids, but their most important role is in the response to …

In the absence of corticosteroids even mild … can be fatal

A

STRESS

38
Q

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

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 the inflammatory response

39
Q

At times of injury:

  • … alerts the sufferer to the damage
  • … dilutes any toxic substances that may be present and immobilises and stabilises …
  • Infiltration by … destroys any invading cells whilst antibodies inactivate the foreign proteins
  • Tissue repair is enhanced by …
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
40
Q
  • In preventing the processes of the inflammatory and immune responses it would appear that the glucocorticoids… the adverse effects of the injury and retard tissue repair
  • The … thus appear to be acting contrary to the individual’s best interests
A
  • In preventing the processes of the inflammatory and immune responses it would appear that the glucocorticoids potentiate the adverse effects of the injury and retard tissue repair
  • The steroids thus appear to be acting contrary to the individual’s best interests
41
Q
  • The adrenocortical stress response decreases the … response
  • It removes the pain and decreases the immobilization induced by the …
  • …-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
A
  • The adrenocortical stress response decreases the inflammatory response
  • It removes the pain and decreases the immobilization 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
42
Q

Summary of the physiological effects of cortisol

  • Stimulates release of amino acids from muscle
    • Increases …lysis
    • Increases …lysis
    • Increase … levels
    • Increase … pressure
    • Direct effects on … and local effects on …
A
  • Stimulates release of amino acids from muscle
    • Increases lipolysis
    • Increases glycogenolysis
    • Increase glucose levels
    • Increase blood pressure
    • Direct effects on brain and local effects on pain
43
Q

Control of mineralocorticoid secretion

  • What are the 2 physiologically important minceralocorticoids?
A
  • Aldosterone and 11-deoxycorticosterone
44
Q
  • The major controlling factor in the secretion of aldosterone is the … system
  • However ACTH stimulates the initial conversion of cholesterol to …
A
  • The major controlling factor in the secretion of aldosterone is the renin-angiotensin system
  • However ACTH stimulates the initial conversion of cholesterol to pregnenolone
45
Q

The secretion of aldosterone is also directly stimulated by what 4 things?

What is it inhibited by?

A
  1. trauma
  2. anxiety
  3. hyperkalaemia
  4. hyponatraemia

inhibited by atrial natriuretic peptide (ANP)

46
Q

Actions of mineralocorticoids

  • Within the circulation aldosterone is only …% protein bound
  • Aldosterone has specific … receptors which cause expression of ion channels that transport … and … ions across the cell membrane
A
  • Within the circulation aldosterone is only 50% protein bound
  • Aldosterone has specific intracellular receptors which cause expression of ion channels that transport sodium and potassium ions across the cell membrane
47
Q
  • Aldosterone stimulates the reabsorption of sodium ions in the … tubule of the kidney, with some lesser effects in the … duct, proximal … and ascending … of …, and in the colon, sweat and … glands
  • The sodium reabsorption occurs in exchange for either … or … 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 of Henle, and in the colon, sweat and salivary glands

48
Q
  • By controlling reabsorption of sodium ions, aldosterone influences plasma .. concentration, which in turn influences water … in the collecting duct via an effect on … secretion.
  • The interaction of the … system, aldosterone and … therefore controls blood … and influences …
A
  • By controlling reabsorption of sodium ions, aldosterone influences plasma .. concentration, which in turn influences water reabsorption in the collecting duct via an effect on ADH secretion.
  • The interaction of the renin-angiotensin system, aldosterone and ADH therefore controls blood volume and influences blood pressure
49
Q

Pharmacological uses of adrenocorticosteroids

  • glucocorticoids (e.g. hydrocortisone = cortisol) are used in … therapy
  • Also used for their immuno… or anti-…. effects in conditions such as …, … or allergies, or for the treatment of proliferative conditions such as …
A
  • glucocorticoids (e.g. hydrocortisone = cortisol) are used in replacement therapy
  • Also used 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
50
Q

Pharmacological uses of mineralocorticoids

  • used only for … therapy
  • … plasma half-life of aldosterone renders it unsuitable for this purpose thus the drug of choice is ….
A
  • used only for replacement therapy
  • short plasma half-life of aldosterone renders it unsuitable for this purpose thus the drug of choice is fludrocortisone
51
Q
  • In most cases the selection of the glucocorticoid is dependent upon the … of the available agents and the predominant effect required
  • Most glucocorticoids are … active but their absorption through the … varies as does their plasma …
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
52
Q

Many adverse effects are associated with the use of glucocorticoids, including:

  1. Steroid usage may suppress … healing and may exacerbate … due to their immunosuppressant effects
  2. Long term use in children may cause what? What about in adults?
  3. The development of … and other symptoms of … syndrome also often accompanies steroid therapy

The most important adverse effect, however, is the suppression of the …-… axis

Chronic administration of exogenous glucocorticoids results in suppression of … secretion leading to atrophy of the adrenal …

A
  1. Steroid usage may suppress wound healing and may exacerbate infections due to their immunosuppressant effects
  2. Long term use in children may cause what? - inhibition of growth What about in adults? - osteoporosis
  3. The development of diabetes mellitus and other symptoms of Cushing’s syndrome also often accompanies steroid therapy
  • The most important adverse effect, however, is the suppression of the hypothalamic-pituitary axis
  • Chronic administration of exogenous glucocorticoids results in suppression of ACTH secretion leading to atrophy of the adrenal cortex
53
Q
  • If steroid therapy is then stopped abruptly, the adrenal cortex is unable to secrete endodenous hormones and the patient suffers with what?
  • How is this overcome
A
  • Addisonian crisis - may be fatal
  • this consequence overcome by the gradual reduction of the dose of the exogenous steroid
54
Q

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

A

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

55
Q

Core drug: Hydrocortisone (Cortisol)

  • Hydrocortisone is a natural … secreted by the adrenal cortex
  • It acts via specific intracellular … receptors to influence gene …
  • Glucocorticoids are typically used for hormone … therapy, as anti-inflammatory agents and immuno….
  • Hydrocortisone is the drug of choice for this therapy
A
  • Hydrocortisone is a natural glucocorticoid secreted by the adrenal cortex
  • It acts via specific intracellular glucocorticoid receptors to influence gene expression
  • Glucocorticoids are typically used for hormone replacementtherapy, as anti-inflammatory agents and immunosuppressants
  • Hydrocortisone is the drug of choice for this therapy
56
Q

Core drug: Hydrocortisone (Cortisol)

  • Oral bioavailability?
  • protein binding?
  • metabolism?
  • half-life?
  • standard dose?
  • adverse effects? (3)
A
  • Oral bioavailability - 60-80%
  • protein binding - high
  • metabolism - hepatic
  • half-life - approx 1.5
  • standard dose - 15-20mg per day in divided doses
  • adverse effects? (3) - hyperglycaemia, osteoperosis, cushing’s syndrome
57
Q

Need to know for adrenal cortex - hormones, physiology

  • synthesis and actions of glucocorticoids, not including synthetic pathway details
  • actions of mineralocorticoids
  • therapeutic uses and adverse effects of corticosteroids
A

:)

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