adrenal gland Flashcards
where are the adrenal glands situated anatomically?
Adrenal glands are situated on the superior pole of the kidney in the retroperitoneal space, each weighing ~4g in adults.
what does the adrenal gland contain?
the adrenal gland is composed of two quite separate endocrine glands rolled into one structure.. adrenal medulla nd cortex
describe the adrenal medulla?
(~25%) is a modified sympathetic ganglion (neuroendocrine gland).
what is the function of the adrenal medulla?
Secretes catecholamines from the postganglionic cell, mainly epinephrine (adrenaline) but also norepinephrine and dopamine.
what is the adrenal cortex?
(~75%), is a true endocrine gland and secretes 3 classes of steroid hormones
what are the three classes of hormones secreted by the adrenal cortex?
Mineralocorticoids e.g. aldosterone: involved in the regulation of Na+ and K+
Glucocorticoids e.g. cortisol: involved in maintaining plasma glucose
Sex steroids e.g. testosterone
what hormones are essential for survival?
Aldosterone and cortisol
what surrounds the adrenal medulla?
Cortex surrounds the medulla and is arranged in 3 concentric zones, producing different hormones.
what are the 3 concentric zones in the adrenal cortex?
Zona glomerulosa → aldosterone
Zona fasciculata → glucocorticoids
Zona reticularis → sex hormones
what hormone does zona glomerulosa produce?
aldosterone
what hormone does zona fasciculata produce?
glucocorticoids
what hormone does zona retiularis produce?
sex hormones
what hormone does the adrenal medulla produce?
Catecholamines
what are all steroid hormones derived from?
how does this relate to synthetic pathways in adrenal cortex?
cholesterol
but different enzymes are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona glomerulosa.
what is a common cause of congenital adrenal hyperplasia?
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 channelled into excessive adrenal androgen production.
describe the hypothalamic pituitary adrenal pathway?
Also short-loop feedback by ACTH on CRH.
Why does a deficit in 21-hydroxylase cause adrenal hyperplasia???
Lack of 21-hydroxylase inhibits synthesis of cortisol.
This removes the negative feedback on ACTH and CRH release.
Increased ACTH secretion is responsible for enlargement of adrenal glands.
Babies become very ill within a few days of birth
what is cortisol?
a glucocorticoid hormone (influences glucose metabolism).
is cortisol bound to a binding protein?
~95% of plasma cortisol is bound to a carrier protein, cortisol binding globulin (CBG).
what do all nucleated cells have?
cytoplasmic glucocorticoid receptors.
once cortisol is bound what happens?
The hormone receptor complex migrates to the nucleus, binding to DNA via a hormone-response element to alter gene expression, transcription and translation.
describe the nature of release of cortisol?
Plasma levels of cortisol show a very characteristic pattern.
There is a marked circadian rhythm, preceded by a similar pattern of release of ACTH.
Cortisol “burst” persists longer than ACTH burst because half-life is much longer.
Peak is ~ 6-9am, nadir (lowest level) is ~ midnight.
Other fluctuations during the day are due to effects of other stimuli which are related to stress.
what does the removal of adrenal glands result in animals?
why?
results in death in a few weeks.
Loss of cortisol means animals cannot deal with stress, particularly in terms of maintaining blood glucose levels.
Cortisol as a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia.
It has a permissive action on glucagon, which is vitals as glucagon alone is inadequate in responding to a hypoglycaemic challenge.
Removal of adrenal glands also renders animals incapable of maintaining their extracellular fluid volume, an effect mediated by aldosterone
how does cortisol help protect the brain from hypoglyceamia?
Cortisol as a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia. It has a permissive action on glucagon, which is vitals as glucagon alone is inadequate in responding to a hypoglycaemic challenge.
what is the action of cortisol on gluconeogensis?
Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle
what is the action of cortisol on proteolysis?
cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver.
what is the action of cortisol on lipolysis?
similarly, cortisol stimulates lipolysis in adipose tissue which increases [FFA] plasma creating an alternative fuel supply that allows [BG] to be protected while also creating a substrate (glycerol) for gluconeogenesis.
what is cortisols effect of insulin senstivity?
Decreases insulin sensitivity of muscles and adipose tissue.
how does cortisol react in comparison to insulin?
cortisol is acting to oppose insulin, not surprisingly ∴ excess cortisol is diabetogenic.
what effect does cortisol have on Calcium balance?
Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption → osteoporosis
what effect does cortisol have on mood and cognition?
depression and impaired cognitive function are strongly associated with hypercortisolaemia.
what effect does cortisol have on norepinephrine?
Permissive effects on norepinephrine: particularly in vascular smooth muscle (α-receptor effect = vasoconstrictive). Cushings Disease (hypercortisolaemia) is strongly associated with hypertension. Likewise, low levels of cortisol are associated with hypotension.
what effect does cortisol have on the immune system?
Suppression of the Immune System: Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response. Latter effect can be useful clinically e.g. asthma/ulcerative colitis/organ transplant.
desribe the negative feedback loop of cortisol?
what are side effects of glucocorticoid therapy?
what happens in withdrawal of chronic glucocorticoid treatment?
Care is required when withdrawing glucocorticoid treatment due to enhanced negative feedback effects of exogenous cortisol.
Additional, therapeutic cortisol enhances the negative feedback on hypothalamus and pituitary reducing release of CRH and ACTH.
Loss of trophic action of ACTH on adrenal gland cause atrophy of gland. Risk of adrenal insufficiency if withdrawal is too fast.
what is aldosterone?
mineralocorticoid
what is the function of aldosterone?
acts on the kidney to determine the levels of minerals reabsorbed/excreted. Aldosterone increases the reabsorption of Na+ ions and promotes the excretion of K+ ions.
what is the secretion of aldosterone by the adrenal cortex primarily controlled by?
complex reflex pathway originating in the kidney, the renin-angiotensin-aldosterone system (RAAS).
what is the effect of increased aldosterone?
release stimulates Na+ (and H2O) retention and K+ depletion, resulting increased blood volume and increased blood pressure.
what is the effect of decreased aldosterone?
Decreased aldosterone leads to Na+ (and H2O) loss and ↑[K+]plasma, resulting in diminished blood volume and decreased blood pressure.
describe cushing syndrome?
hypersecretion of cortisol
tumour in adrenal cortex (1o hypercortisolism = Cushing’s syndrome)
describe cushings disease?
pituitary gland (2o hypercortisolism = Cushing’s disease). Most common. Excess ACTH.
what is cushings disease characterised by?
Cushing’s Disease is characterised by wasting of the extremities (due to catabolic action of cortisol) but for unknown reasons fat is redistributed to the face (“moon face”) and trunk.
what can cause hyposecretion of aldosterone?
Addison’s disease
Hyposecretion of all adrenal steroid hormones
Due to autoimmune destruction of adrenal cortex
Hyperpigmentation due to xs MSH stimulation of melanocytes (in 1o disorders). MSH is produced from same precursor as ACTH so as ACTH levels increase, so do MSH
Hypotension due to loss of permissive effect of cortisol on adrenoceptors AND loss of ability to retain Na+ leading to hypovolaemia
Addisonian Crisis/Adrenal crisis – life threatening hypotension and hypoglycaemia. Medical emergency. - loss of cortisol and minerocortisol steroids
what promotes CRH and ACTH release?
CRH and ACTH release is promoted by stress.
what disinhibits the Hypothalamo-Pituitary-Adrenal Axis (HPA)?
Alcohol, caffeine and lack of sleep
Alcohol in particular depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH.
does elevation of cortisol levels have a imoact on vunerability to infection?
Subsequent elevation of cortisol levels effectively turn down the immune system, increasing vulnerability to infection.
adrenal medulla
Modified sympathetic ganglion, not true endocrine tissue. Similar to posterior pituitary in having neuroendocrine role.
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.
what is Pheochromocytoma?
a rare neuroendocrine tumour, found in adrenal medulla which results in XS catecholamines: ↑HR→↑CO →↑↑BP
Diabetogenic due to adrenergic effect on glucose metabolism.
Responds well to surgery.
secondary hypersecretion due to a hypothalamic problem?
secondary hypersecretion due to a pituitary problem?
primary hypersecretion due to probem with adrenal cortex?
