HPA axis and adrenal hormones Flashcards
What is the adrenal axis (hypothalamic-pituitary-adrenal axis)?
Complex set of interaction and feedback loops between the hypothalamus, pituitary, and adrenal glands. It regulates the body’s response to stress, immune function, energy expenditure, mood, emotions and libido.
Where are the adrenal glands located?
Just above each kidney
What are the hormones released from the adrenal glands?
Cortisol, aldosterone, adrenaline and noradrenaline.
What are adrenal glands composed of?
Outer cortex and an inner medulla
What are 3 classes of steroid hormones produced and released into the circulation by the adrenal cortex?
Mineralocorticoids – mainly aldosterone
Glucocorticoids – mainly cortisol (hydrocortisone)
Androgens – sex hormones
What does the adrenal inner medulla produce?
Adrenaline and noradrenaline through direct control of the hypothalamus.
What are the effects of adrenaline and noradrenaline?
Fight or flight response. Increased heart rate, blood pressure and muscle perfusion.
What ions do steroids have an effect on?
Increased Na reabsorption
Increased K secretion
Aldosterone regulation half-life?
20 mins (short)
What are the two effects that aldosterone is regulated by?
Direct Indirect (most important)
What is direct effects on aldosterone stimulated by?
Stimulated by low plasma Na or K (action on zona glomerulosa cell of adrenal cortex)
What is indirect effects on aldosterone stimulated by?
Stimulated by angiotensin II (renin angiotensin system)
Aldosterone regulation (5)
- Low blood volume stimulates the release of angiotensin II.
- Angiotenis II stimulates the adrenal cortex to produce aldosterone.
- Aldosterone has a number of different action including: sodium reabsorption, water reabsorption, potassium excretion]
- Aldosterone, therefore, causes a net increase in blood volume
- Increased blood volume inhibits the production of angiotensin II via negative feedback.
What is aldosterone?
A mineralocorticoids that regulates Na and K.
What does aldosterone act on to regulate Na and K?
Mineralocorticoid receptors in distal tubules increase Na reabsorption and K secretions.
What are the effects of no aldosterone?
Low Na and High K Leads to depolarization of plasma membrane Cardiac arrythmia Muscle weakness Hypotension
What does adrenal hypersecretion cause?
Conn’s syndrome
Symptoms of aldosterone hypersecretion (Conn’s syndrome)
Hypertension
High Na
Low K
Oedema (water retention)
Treatment of aldosterone hypersecretion?
MR (Mineralocorticoid receptors) antagonist/aldosterone antagonist
- spironolactone – lack of selectivity leads to side effects
- Eplerenone – fewer side effects
What does adrenal hyposecretion cause?
Addison’s syndrome
Symptoms of aldosterone hyposecretion (Addison’s syndrome)
Hypotension and vascular collapse Low NA dehydration High K Cardiac arrythmias Potentially fatal
Treatment of aldosterone hyposecretion?
Mineralocorticoid agonist
Fludrocortisone – longer half-life than aldosterone
Why is aldosterone inappropriate for treatment for hyposecretion?
Short aldosterone half-life means it is not used for drug treatment
What other things use fludrocortisone as treatment?
Postural hypotension or symptomatic hypotension treatment involves fludrocortisone
Cortisol half life
90 minutes
What are the three effects that cortisol is regulated by?
- Metabolic (physiological)
- Anti-inflammatory (supraphysiological)
- Immunosuppressive (supraphysiological)
What does cortisol act on?
Glucocorticoid receptors to regulate transcription
What are the metabolic effects of cortisol?
- Liver - Glucose production (gluconeogenesis)
- Skeletal muscle - Increase in protein degradation (Increased a.a.)
- Adipose tissue - Increased lipolysis (Increased free fatty acids and glycerol for gluconeogenesis)
- Bone - Matrix protein breakdown (Increased a.a. for gluconeogenesis)
- Mobilisation of energy stores in time of stress
Where are the metabolic effects of cortisol? (5)
- Liver
- Skeletal muscle
- Adipose tissue
- Bone
- Mobilisation of energy stores in time of stress
What is the metabolic effect in the Liver?
- Glucose production (gluconeogenesis)
What is the metabolic effect in the Skeletal muscle?
- Increase in protein degradation (Increased a.a.)