Flashcards in Adrenal cortex: Hormones, physiology Deck (23)
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1
Glucocorticoids
- Synthesis
- Control of secretion
- Example
Synthesised by cells of the zona fascicularis
- 17a hydoxylase enzyme
- From cholesterol
Secretion stimulated by:
- Stimulated by ACTH
- Stress
Inhibited by
- Negative feedback
Example
- Cortisol
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Mineralocorticoids
- Synthesis
- Control of secretion
- Example
Synthesised by cells of the glomerulosa
- 18-hydroxylase
- From cholesterol
Control of secretion
- RAAS control
Example
- Aldosterone
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Adrenal androgens
- Synthesis
- Control of secretion
- Example
Synthesised by cells of the zone reticularis
- Using 17a-hydroxylase
- From cholesterol
Control of secretion
- regulated by ACTh release
Example
- Testosterone in very small amounts
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Cortisol and ACTH diurnal variation
Cortisol levels peak after a delay, when there is an increase in ACTH initially
- Due to slow action of hormones
Cortisol and ACTH peak in the early morning.
Cortisol nadir is 2 hrs later than ACTH in the night.
- Negative feedback
5
Cortisol and stress
Stress from injury, trauma, psychological, hypoglycaemia, illness triggers CRH and ACTH release rapidly.
- High ACTH levels amplifies effects of cortisol.
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Transport of corticosteroids [3]
Not water soluble---> Only 10% free.
75%---> Corticosteroid binding globulin/ transcortin.
15%----> Bound to albumin
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Transport of corticosteroids in pregnancy
CBG levels increase
- Causes increase in plasma cortisol
- Free cortisol level still stable.
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Metabolism of steroid hormones
In the liver
- Glucuronidation to make water soluble
- Excreted in via kidney in urine.
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Action of cortisol at normal levels
Inhibits insulin's action of cellular glucose intake.
Promotes glycogenolysis.
Promotes hepatic gluconeogenesis by increasing amino acid uptake.
Lipolysis and fatty acid mobilisation.
- Potentiates GH and catecholamines.
Causes elation/ sedation.
Vasoconstriction
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Action of XS cortisol levels
Fatty acid synthesis and deposition at
- Face
- Trunk
- Intrascapular region
Inhibits the uptake of amino acids in the periphery
- Inhibits skeletal muscle protein synthesis.
11
11-beta hydroxysteroid dehydrogenase
Enzyme that converts cortisol into cortisone.
- Does so in aldosterone sensitive tissue as cortisol can bind to mineralocorticoid receptors.
12
Immunological effects of corticosteroids.
Overall---> Suppresses the immune system.
- Allows function, despite injury/illness.
- Suppresses lymphoid tissue---> Reduced production of antibodies.
- Inhibits cellular function of immunological cells.
- Inhibits proteolytic enzymes that act as inflammatory mediators
- Inhibits phospholipase-A2---> inhibits prostaglandins formation.
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Corticosteroids effects on injury/ Stress
Removes inflammation of injury, but does not help to redeem the underlying cause of injury.
- Inhibits tissue repair
Reduces inflammation reduces oedema
- Allows mobilisation of limbs
Sedation stimulated
- Relieves pain= more mobilisation of limbs.
14
Addison's crisis
Hypoadrenalism
- Very low cortisol levels
Can occur when long-term treatment of corticosteroids is stopped abruptly.
- Cortex stops producing hormones.
- Fatal within 48 hrs.
15
Mineralocorticoid pharmacological uses
- Example
Replacement therapy
- e.g fludrocortisol
- Hypoaldosteronism treatment.
- Addison's disease treatment
Aldosterone not used as it has a short plasma-half life.
NOT used as an immunosuppressant, does not have major immunological effects.
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Glucocorticoids pharmacological uses
- Examples
- Conditions treated
Replacement therapy
- Addison's disease/ adrenal insufficiency.
Immunosuppressant/ anti-inflammatory
- Asthma
- Arthritis
- Leukaemia
- Allergies
Examples
- Hydrocortisone [cortisol]
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Adverse effects of glucocorticoids [5]
Impairs wound healing/ tissue repair
- Can make injuries worse.
Inhibits growth in children.
- Inhibits peripheral protein synthesis
Osteoporosis in adults.
Excess cortisol
- Cushing's
- Diabetes [hyperglycaemic properties]
Adrenal cortex atrophy
- Negative feedback of HPA axis.
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Hydrocortisone
- Drug type
- Mechanism
- Use
- Standard dose
Glucocorticoid
[cortisol]
Mechanism
- Minds to intracellular receptors to influence gene expression
- Causes anti-inflammation and immunosuppression.
Use:
- Hormone replacement therapy: primary adrenal insufficiency
- Thyrotoxic crisis
- Anti-inflammatory
- Anaphylaxis
- Asthma, leukaemia, arthritis, allergies, eczema
Standard dose [replacement therapy]
- 15-20mg
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Hydrocortisone
- Bioavailability
- Protein binding
- Metabolism
- Half life
Bioavailability: fairly high
- 60-80%
Protein binding: not water soluble
- HIGH
Metabolism
- Hepatic
Half-life
- 1.5hrs.
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Hydrocortisone
- Adverse effects [3]
Hyperglycaemia
Osteoporosis
Cushing's
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Mineralocorticoid secretion
- Triggers
- Inhibitors
Majorly influenced by the RAS.
- Production of Angiotensin II triggers secretion
Trigger---> Low BP
- Dehydration
- Haemorrhage
Other stimulators
- Trauma
- Anxiety
- Hyperkalaemia
- Hyponatraemia
Inhibitor
- ANP
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Mineralocorticoid action
Aldosterone acts on intracellular aldosterone receptors in kidney tubule
- Insertion of Na+ and K+ channels in DT [mainly], CD, PT, ascending loop.
Also acts to reabsorb Na+ in
- colon
- sweat glands
- salivary glands
Increased Na+ in plasma triggers ADH release
- Absorbs water via aquaporins= increase BP
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