L5 - Adrenal Cortex COPY

Question 1

ANATOMY OF THE ADRENAL GLANDS

i) what % of the adrenals is medulla and what % is cortex?
ii) what is the medulla primarily concerned with?
iii) what is the cortex primarily concerned with? (3)
iv) which part of the adrenal gland is essential for life?

Answer 1

i) medulla is 10% and cortex is 90%
ii) medulla is associated with stress response
iii) cortex is associated with stress, sodium and glucose
iv) the adrenal cortex is essential for life

Question 2

SYNTHESIS OF ADRENAL HORMONES

i) what are the three layers of the adrenal cortex?
ii) what type of hormones does the cortex synthesise?
iii) name the two mains types of these and give an example of each

Answer 2

i) zona glomerulosa - outer
zona fasciculata - middle
zona reticularis - inner

ii) adrenal cortex synthesises steroid hormones from cholesterol
iii) two main types are glucocorticoids (cortisol) and mineralocorticoids (aldosterone)

Question 3

SYNTHETIC PATHWAY OF STEROID HORMONES

i) what is the common precursor for all steroid hormones?
ii) what three pathways can be taken and what is the end result of each?
iii) which enzyme is required for the production of GCs and androgens?
iv) which hormone does the zona glomerulosa produce? why?
v) which two hormone classes can be produced by zona fasciculata and reticularis? why?
vi) which layer of the cortex is a) cortisol and b) androgens synthesised in?

Answer 3

i) cholesterol
ii) mineralocorticoid (aldosterone), glucocorticoid (cortisol) and androgen (testosterone/estradiol)
iii) 17a-hydroxylase enzyme is required to make GCs and androgens
iv) ZG produces only MCs (aldosterone) as it does not have the 17a-hydroxylase enzyme
v) ZF and ZR can produce GCs and androgens as they have the 17aOH enzyme

vi) cortisol is prod in zona fascic CF
androgens are prodc in the zona retic RA

Question 4

HORMONE SECRETION

i) what level of androgen/oestrogens are secreted from the adrenal cortex under normal circumstances?
ii) what level is secreted in adrenal disorders?
iii) name three male androgens and one female oestrogen released from the adrenal cortex

Answer 4

i) small amounts
ii) larger amounts

iii) male = DHEA, androstenedione and testosterone
female = estradiol

Question 5

CONTROL OF GLUCOCORTICOID SECRETION

i) which hormones are released from the hypothalamus and anterior pit gland to induce cortisol secretion?
ii) where does cortisol feedback to once produced?
iii) what is the character of secretion of ACTH? what time of day is it highest and lowest?
iv) in which situation may there be increased secretion of ACTH?
v) when does cortisol peak and trough in relation to ACTH?
vi) name two things that may disrupt these patterns of hormone release

Answer 5

i) HT releases CRH which causes ant pit to release ACTH which causes adrenal to release cortisol
ii) cortisol has negative feedback back to the HT and CRH release

iii) ACTH secretion is pulsatile
- highest in the morning at time of waking
- lowest in the middle of the night

iv) Increased secretion of ACTH in times of prolonged stress
v) cortisol follows a similar release pattern to ACTH but peaks and troughs two hours later
vi) shift work and long haul travel can disrupt these patterns

Question 6

TRANSPORT OF GLUCOCORTICOIDS

i) what % of cortisol is in the free active form in the blood?
ii) how does the remainder travel? name the two compnents of this and %s
iii) what protein is increased in pregnancy? what does this result in in relation to circulating plasma conc of cortisol and free cortisol?

Answer 6

i) 10%

ii) the rest travels bound to proteins
- CBG (corticosteroid binding globulin) 75%
- albumin (15%)

iii) increase in CBG in pregnancy
- results in a compensatory increase in circulating plasma cortisol concs (bound to proteins)
- free cortisol remains stable

Question 7

METABOLISM OF ADRENAL STEROIDS

i) which organ does it predominantly occur in?
ii) what process happens here? what is the solubility of the end product?
iii) how are they excreted?

Answer 7

i) metabolism occurs in the liver
ii) glucuronidation and the product is water soluble
iii) excreted in the urine

Question 8

ACTION OF CORTISOL - CARBOHYDRATES

i) what is the most important action of cortisol at normal physiological concentrations?
ii) which hormone does cortisol work in opposition to?
iii) name two effects cortisol when working in this opposition
iv) what effect does it have on GLUT4? what does this cause?

Answer 8

i) action on carbohydrate metabolism - RAISES blood glucose
ii) works in opposition to insulin

iii) stimulates glycogenolysis
stimulates hepatic gluconeogenesis

iv) inhibits GLUT4 so decreases the amount of glucose taken up by cells

Question 9

ACTION OF CORTISOL - FATS

i) what two effects does cortisol have on fats?
ii) which two hormones are used for this?
iii) what can excessive concs of cortisol cause in relation to fats? (2)
iv) what condition is this analogous too? give two reasons why

Answer 9

i) stimulates lipolysis and mobilisation of fatty acids
ii) uses growth hormone and catecholamines
iii) excess cortisol = fat synthesis and fat deposition at novel sites (face, trunk, intrascap region)
iv) analagous to cushings = large round face and central obesity

Question 10

ACTION OF CORTISOL AROUND THE BODY

i) what effect does cortisol have on amino acids in the liver? what does this lead to?
ii) what effect does cortisol have on amino acids in the periphery? what does this lead to?
iii) what condition is the above effect seen in?

Answer 10

i) causes stimulation of amino acid uptake in the liver
- leads to gluconeogenesis

ii) causes inhibition of amino acid uptake in the periphery and reduced protein synthesis
- leads to a net loss of skeletal protein

iii) loss of skeletal protein seen in Cushings syndrome
- see proximal muscle weakness

Question 11

GLUCOCORTICOID ACTION

i) which non GC receptors can GCs also stimulate?
ii) what enzyme is present in aldosterone sensitive tissues that may stop this from happening?
iii) what concentration of GCs are required to have MC action?
iv) what is the effect of excess cortisol in response to catecholamines? what does this result in?
v) what feelings can be evoked when GCs act on the brain?

Answer 11

i) aldosterone (MC) receptors
ii) 11-b-HSD1 - converts cortisol to inactive cortisone
iii) need high GC concs to have MC actions
iv) excess cortisol = enhanced vasoconstrictor responses to catecholamines which can lead to high BP
v) can produce psychological effects with feelings of elation or sedation

Question 12

GLUCOCORTICOIDS AND THE IMMUNE SYSTEM

i) what effect do GCs have on lymphoid tissue, antibody production and the cellular immune system?
ii) what effect do GCs have on leucocyte membranes and proteolytic enzymes
iii) what effect do GCs have on phospholipase A2 and other inflammatory mediators
iv) what is the ultimate effect of GCs on the imm sys?

Answer 12

i) supress lymphoid tissue and antibody production
- inhibit the cellular immune response

ii) stabilise leucocyte membranes and reduce release of proteolytic enzymes
iii) inhibit phospholipase A2 and reduce synth of other inflamm mediators
iv) REDUCE IMMUNE SYSTEM FUNCTIONING

Question 13

GLUCORTICOIDS AND STRESS

i) what can happen during mild stress, in the absence of GCs?
ii) what do GCs do in times of prolonged stress? (2)
iii) what effect do GCs have on injury effects and tissue repair?
iv) name four things that the stress response does in times of injury
v) what do all these effects allow?

Answer 13

i) mild stress can be fatal
ii) prolonged stress - GCs maintain enhanced supply of glucose and supress the inflammatory response
ii) GCs potentiate adverse effects of injury and prevent tissue repair
v) removes pain, decreases immobilisation caused by oedema, steroid induced sedation, lack of awareness of severity of the situation
v) effects allow the individual to perform, despite the presence of injury or infection

Question 14

SUMMARY OF PHYSIOL EFFECTS OF CORTISOL

i) what effect does it have on the liver
ii) on fat
iii) on blood pressure

Answer 14

i) increases substrates for the liver to make glucose
ii) increases lipolysis
iii) increases blood pressure

Question 15

CONTROL OF MINERALOCORTICOID SECRETION

i) name two physiologically important mineralocorticoids
ii) what system is the major controlling factor in secretion of aldosterone?
iii) which hormone stimulates the initial conversion of cholesterol to pregnenolone?
iv) name four things that directly stimulate aldosterone secretion and one thing that inhibits it

Answer 15

i) aldosterone and 11-deoxycorticosterone (precursor)
ii) renin angiotensin system
iii) ACTH

iv) aldo is stim by trauma, anxiety, hyperkalemia and hyponatremia (low Na)
inhibuted by atrial natriuretic peptide (ANP)

Question 16

ACTION OF MINERALOCORTICOIDS

i) what % of aldosterone is protein bound in the circulation?
ii) where are aldosterone receptors found? what does activation of these receptors generally cause?
iii) what does aldosterone stimulate in the kidney? which area in particular?
iv) what does the action of aldosterone also influence? what hormone is involved in this?
v) the interaction of the renin angiotensin system with which two hormones controls blood volume and BP?

Answer 16

i) 50%

ii) intracellular
- causes expression of ion channels (Na/K pumps) that allow Na into the cell/blood and K+ out (also H+ out)

iii) stimulates Na reabs in the distal tubule (via Na/K pump)
also in CD (via ENaC), prox tub, LOH, colon, sweat and salivary glands

iv) aldo also influences water reabs in the CD via ADH secretion
v) RAAS ineracts with aldosterone and ADH to increase blood volume and blood pressure

Question 17

PHARMA EFFECTS OF GLUCOCORTICOIDS

i) what type of therapy are GCs used for? is this the only thing they are used for?
ii) what two effects may GCs have? which conditions are they therefore used in? (3)
iii) GCs are used in proliferative conditions such as leukaemia - true or false?
iv) name a condition that may need hydrocortisone x3 daily. why?
v) what form are most GCs active in? which route of admin may also be used?

Answer 17

i) used in replacement therapy
- they are also used for their immunosupp/anti-inflam effects

ii) GCs - immunosupp and anti-inflam
- used in arthritis, asthma and allergies

iii) true
iv) addisons disease (non func adrenal cortex due to autoimm or TB)
v) most GCs are orally active but may also be used transdermal

Question 18

PHARMA EFFECTS OF MINERALOCORTICOIDS

i) what is their sole use in?
ii) why is aldosterone unsuitable for this type of therapy?
iii) what is the drug of choice?
iv) when may this be used?

Answer 18

i) replacement therapy
ii) aldo is unsuitable as it has a short plasma half life
iii) drug of choice is fldrocortisone
iv) used for replacement of loss of MC function eg in an adrenal infarct

Question 19

ADVERSE EFFECTS OF GLUCOCORTICOIDS

i) how may they impact on wound healing and infections?
ii) what can long term use in children cause? what about adults?
iii) development of which endocrine condition can accompany steroid therapy?
iv) symptoms of which syndrome may accompany steroid therapy that is being given at high doses for a long time?
v) chronic admin of GCs can suppress which axis? which hormone is implicated? what does this cause in the adrenal cortex?
vi) what may happen if steroid therapy is stopped abruptly? how is this overcome?

Answer 19

i) supress wound healing and exacerbate infections as they are immunosupp

ii) LT use in children = inhibition of growth
in adults = osteoporosis

iii) steroid therapy can lead to dev of T2DM
iv) symptoms of cushings may accompany

v) chronic admin can supress the hypothalamic pit axis
- supression of ACTH which leads to atrophy of the adrenal cortex (addisons)

vi) abrupt termination can cause an addisons crisis (adrenal cortex is unable to secrete endog hormone)
- avoid this by gradually reducing dose of exog steroid

Question 20

CORE DRUG: HYDROCORTISONE

i) what is it aka?
ii) what does it influence when bound to receptor?
iii) name three typical uses
iv) what type of therapy is it the drug of choice for? what condition would this be used in?
v) what is its oral bioavail and level of protein binding?
vi) how is it metabolised, excreted and what is its half life?
vii) name three adverse effects

Answer 20

i) cortisol
ii) influences gene expression once bound to GC receptor
iii) used in HRT, anti-inflamm and immunosuppresion
iv) drug of choice for replacement therapy eg in addisons
v) 60-80% oral bioavil and high protein binding

vi) metab by the liver
half life 1.5hrs
excreted urine and faeces

vii) hyperglycaemia, osteoporosis and cushings syndrome