adrenal gland

Question 1

where are the adrenal glands situated anatomically?

Answer 1

Adrenal glands are situated on the superior pole of the kidney in the retroperitoneal space, each weighing ~4g in adults.

Question 2

what does the adrenal gland contain?

Answer 2

the adrenal gland is composed of two quite separate endocrine glands rolled into one structure.. adrenal medulla nd cortex

Question 3

describe the adrenal medulla?

Answer 3

(~25%) is a modified sympathetic ganglion (neuroendocrine gland).

Question 4

what is the function of the adrenal medulla?

Answer 4

Secretes catecholamines from the postganglionic cell, mainly epinephrine (adrenaline) but also norepinephrine and dopamine.

Question 5

what is the adrenal cortex?

Answer 5

(~75%), is a true endocrine gland and secretes 3 classes of steroid hormones

Question 6

what are the three classes of hormones secreted by the adrenal cortex?

Answer 6

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

Question 7

what hormones are essential for survival?

Answer 7

Aldosterone and cortisol

Question 8

what surrounds the adrenal medulla?

Answer 8

Cortex surrounds the medulla and is arranged in 3 concentric zones, producing different hormones.

Question 9

what are the 3 concentric zones in the adrenal cortex?

Answer 9

Zona glomerulosa → aldosterone
Zona fasciculata → glucocorticoids
Zona reticularis → sex hormones

Question 10

what hormone does zona glomerulosa produce?

Answer 10

aldosterone

Question 11

what hormone does zona fasciculata produce?

Answer 11

glucocorticoids

Question 12

what hormone does zona retiularis produce?

Answer 12

sex hormones

Question 13

what hormone does the adrenal medulla produce?

Answer 13

Catecholamines

Question 14

what are all steroid hormones derived from?

how does this relate to synthetic pathways in adrenal cortex?

Answer 14

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.

Question 15

what is a common cause of congenital adrenal hyperplasia?

Answer 15

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.

Question 16

describe the hypothalamic pituitary adrenal pathway?

Answer 16

Also short-loop feedback by ACTH on CRH.

Question 17

Why does a deficit in 21-hydroxylase cause adrenal hyperplasia???

Answer 17

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

Question 18

what is cortisol?

Answer 18

a glucocorticoid hormone (influences glucose metabolism).

Question 19

is cortisol bound to a binding protein?

Answer 19

~95% of plasma cortisol is bound to a carrier protein, cortisol binding globulin (CBG).

Question 20

what do all nucleated cells have?

Answer 20

cytoplasmic glucocorticoid receptors.

Question 21

once cortisol is bound what happens?

Answer 21

The hormone receptor complex migrates to the nucleus, binding to DNA via a hormone-response element to alter gene expression, transcription and translation.

Question 22

describe the nature of release of cortisol?

Answer 22

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.

Question 23

what does the removal of adrenal glands result in animals?

why?

Answer 23

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

Question 24

how does cortisol help protect the brain from hypoglyceamia?

Answer 24

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.

Question 25

what is the action of cortisol on gluconeogensis?

Answer 25

Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle

Question 26

what is the action of cortisol on proteolysis?

Answer 26

cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver.

Question 27

what is the action of cortisol on lipolysis?

Answer 27

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.

Question 28

what is cortisols effect of insulin senstivity?

Answer 28

Decreases insulin sensitivity of muscles and adipose tissue.

Question 29

how does cortisol react in comparison to insulin?

Answer 29

cortisol is acting to oppose insulin, not surprisingly ∴ excess cortisol is diabetogenic.

Question 30

what effect does cortisol have on Calcium balance?

Answer 30

Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption → osteoporosis

Question 31

what effect does cortisol have on mood and cognition?

Answer 31

depression and impaired cognitive function are strongly associated with hypercortisolaemia.

Question 32

what effect does cortisol have on norepinephrine?

Answer 32

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.

Question 33

what effect does cortisol have on the immune system?

Answer 33

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.

Question 34

desribe the negative feedback loop of cortisol?

Answer 34

Question 35

what are side effects of glucocorticoid therapy?

Answer 35

Question 36

what happens in withdrawal of chronic glucocorticoid treatment?

Answer 36

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.

Question 37

what is aldosterone?

Answer 37

mineralocorticoid

Question 38

what is the function of aldosterone?

Answer 38

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.

Question 39

what is the secretion of aldosterone by the adrenal cortex primarily controlled by?

Answer 39

complex reflex pathway originating in the kidney, the renin-angiotensin-aldosterone system (RAAS).

Question 40

what is the effect of increased aldosterone?

Answer 40

release stimulates Na+ (and H2O) retention and K+ depletion, resulting increased blood volume and increased blood pressure.

Question 41

what is the effect of decreased aldosterone?

Answer 41

Decreased aldosterone leads to Na+ (and H2O) loss and ↑[K+]plasma, resulting in diminished blood volume and decreased blood pressure.

Question 42

describe cushing syndrome?

Answer 42

hypersecretion of cortisol tumour in adrenal cortex (1o hypercortisolism = Cushing’s syndrome)

Question 43

describe cushings disease?

Answer 43

pituitary gland (2o hypercortisolism = Cushing’s disease). Most common. Excess ACTH.

Question 44

what is cushings disease characterised by?

Answer 44

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.

Question 45

what can cause hyposecretion of aldosterone?

Answer 45

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

Question 46

what promotes CRH and ACTH release?

Answer 46

CRH and ACTH release is promoted by stress.

Question 47

what disinhibits the Hypothalamo-Pituitary-Adrenal Axis (HPA)?

Answer 47

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.

Question 48

does elevation of cortisol levels have a imoact on vunerability to infection?

Answer 48

Subsequent elevation of cortisol levels effectively turn down the immune system, increasing vulnerability to infection.

Question 49

adrenal medulla

Answer 49

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.

Question 50

what is Pheochromocytoma?

Answer 50

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.

Question 51

secondary hypersecretion due to a hypothalamic problem?

Answer 51

Question 52

secondary hypersecretion due to a pituitary problem?

Answer 52

Question 53

primary hypersecretion due to probem with adrenal cortex?

Answer 53