Lecture 6: The Adrenal Gland Flashcards
the adrenal gland is composed of which two endocrine glands (rolled into one structure)?
- adrenal medulla (25%) is a modified sympathetic ganglion (neuroendocrine gland).
- adrenal cortex (75%), is a true endocrine gland.
what does the adrenal medulla secrete?
catecholamines from the post-ganglionic cell, mainly epinephrine (adrenaline) but also norepinephrine and dopamine.
what does the adrenal cortex secrete?
3 classes of steroid hormones:
1. mineralocorticoids e.g. aldosterone: involved in regulation of Na+ and K+.
2. glucocorticoids e.g. cortisol: involved in maintaining plasma glucose.
3. sex steroids e.g. testosterone
aldosterone and cortisol are essential for survival
which zone of the adrenal cortex secretes sex hormones?
zona reticularis
which zone of the adrenal cortex secretes glucocorticoids e.g. cortisol?
zona fasciculata
which zone of the adrenal cortex secretes aldosterone?
zona glomerulosa
defects in 21-hydroxylase is a common cause of?
- congenital adrenal hyperplasia resulting in deficiency of aldosterone and cortisol and associated disruption of salt and glucose balance.
- androgen biosynthesis is unaffected so accumulating steroid precursors are channeled into excessive adrenal androgen production. increased ACTH secretion responsible for enlargement
what is the peak time for plasma cortisol levels?
6-9am
why is cortisol essential for life?
- loss of cortisol means animals cannot deal with stress, particularly in terms of maintaining blood glucose levels.
- cortisol is crucial in helping to protect the brain from hypoglycaemia.
- it has a permissicve action on glucagon, which is vital al glucagon alone is inadequate in responding to hypoglycaemic challenge.
list the actions of cortisol on glucose metabolism (glucocorticoid actions)
- gluconeogenesis: cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis.
- proteolysis
- lipolysis: creates an increase [FFA plasma] creating an alternative fuel supply that allows [BG] to be protected whilst also creating a substrate (glycerol) for gluconeogenesis.
- decreases insulin sensitivity of muscles and adfipose tissue.
list the additional (non-glucocorticoid) actions of cortisol
- negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption > osteoporosis.
- impairment of mood and cognition
- permissive effects on norepinephrine: particularly in vascular smooth muscle (alpha-receptor effect = vasoconstrictive). Cushing’s disease (hypercortisolaemia) is strongly associated with hypertension.
- suppression of the immune system: can be useful clinically e.g. asthma, UC, organ transplant.
what are side effects of glucocorticoid (e.g. cortisol) therapy?
- increased severity and frequency of infection due to immune system suppression.
- muscle wastage due to proteolysis.
- loss of percutaneous fat stores gives appearance of ‘thinning skin’ making it more fragile due to lipolysis.
what can happen when withdrawing chronic glucocorticoid treatment too quickly?
- exogenous cortisol has enhanced negative feedback effects on ACTH and CRH.
- loss of trophic action of ACTH on adrenal gland > atrophy of gland > adrenal insufficiency.
what is the function of aldosterone?
- aldosterone is a mineralocorticoid, which acts on the kidney to determine the levels of minerals reabsorbed/excreted.
- aldosterone increases the reabsorption of sodium ions and promotes the excretion of potassium ions.
- aldosterone is essential for life.
what are the effects of increased aldosterone release?
- stimulates Na+ (and H2O) retention and K+ depletion, resulting in increased blood volume and **increased blood pressure. **
what are the effects of decreased aldosterone release?
- leads to Na+ (and H2O) loss and increased plasma [K+], resulting in diminished blood volume and **decreased blood pressure. **
list the causes of Cushing’s syndrome/disease
Hypersecretion is most commonly due to a tumour in:
- adrenal cortex (primary hypercortisolism = Cushing’s syndrome) or
- pituitary gland (secondary hypercortisolism = Cushing’s disease, most common, excess ACTH)
- Iatrogenic: too much cortisol administered therapeutically.
what is the appearance of Cushing’s disease characterised by?
- wasting of extremities (due to catabolic action of cortisol)
- for unknown reason, fat is redistributed to the face (‘moon face’) and trunk.
describe Addison’s disease
- hyposecretion of all adrenal steroid hormones (hyposecretion of cortisol).
- due to immune destruction of adrenal cortex.
what is an Addisonian crisis/adrenal crisis?
- life threatening hypotension and hypoglycaemia.
- medical emergency.
how does stress increase vulnerability to infection?
- CRH and ACTH release is promoted by stress
- 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 stres effect and increasing levels of CRH and ACTH.
- subsequent elevation of cortisol levels > immune suppression > increased vulnerability to infection.
describe the adrenal medulla
- modified sympathetic ganglion, not true endocrine tissue.
- preganglionic sympathetic fibres 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.
describe pheochromocytoma
- a rare neuroendocrine tumour, found in the adrenal medulla which results in excess catecholamines (e.g. epinephrine, norepinephrine).
- this causes increased heart rate, increased cardiac output, increased blood pressure.
- diabetogenic due to adrenergic effect on glucose metabolism.
- responds well to surgery.
what are the levels of CRH, ACTH and cortisol when there is secondary hypersecretion in due to pathology in hypothalamus?
CRH - high
ACTH - high
cortisol - high
what are the levels of CRH, ACTH and cortisol when there is secondary hypersecretion due to pathology in the anterior pituitary?
CRH- low
ACTH- high
cortisol- high
what are the levels of CRH, ACTH and cortisol when their is primary hypersecretion due to pathology in adrenal cortex?
CRH > low
ACTH > low
cortisol > high
