adrenal gland Flashcards
What are the 3 layers to the adrenal cortex? (from outside to in)
- zona glomerulosa
- zona fasiculata
- zona reticularis
What type of cells are found within the adrenal medulla?
chromaffin cells
Where are glucocorticoids, mineral corticoids and androgens released from?
- mineralcorticoids from zona glomerulosa
- glucocorticoids from zona faculata
- androgens and glucocorticoids from zona reticularis
State the main mineralcorticoids, glucocorticoids and androgens
- mineralcorticoids: aldosterone
- glucocorticoids: cortisol (also cortisone)
- androgens: DHEA, androstenedione- becomes testosterone and ostrogen
What type of hormones are glucocorticoids, mineralcorticoids, androgens, oestrogens and progestins?
steroids (derived from cholesterol)
How do steroids exert their effects?
theyre lipid soluable so enter cell, bind to nuclear receptors and modulate gene transcription
Describe how corticosteroids regulate gene transcription
- they diffuse across plasma membrane
- bind to receptors (which have chaperone proteins attached)
- binding dissociates chaperones
- receptor/ ligand complex moves into nucleus
- can dimerise with other receptors and bind to glucocoritcoid response elements
- or bind to transcription factors
- both regulate expression
How does aldosterone travel in blood?
mostly bound to albumin but some binds to transcortin (another carrier protein)
What does aldosterone do?
increases expression of Na/K pump in distal tubules and collecting ducts of nephron which leads to more reabsobtion of Na and so water and excretion of K+. More water in blood leads to higher blood pressure
What is the difference between primary and secondary hyperaldosteronism? Give some examples of each
primary: defect in adrenal cortex (bilateral idiopathic adrenal hyperplasia is most common, also conns syndrome)
secondary: due to overactivity of RAAS (renin producing tumour (rare), renal artery stenosis)
What is conns syndrome?
an aldosterone secreting adrenal adenoma
How can you distinguish between primary and secondary hyperaldosteronism?
primary: LOW RENIN
secondary: HIGH RENIN
What are signs of hyperaldosteronism?
high blood pressure (esp in young) LV hypertrophy Stroke Hypernaturaemia (High Na+) Hypokalaemia (Low K+) also headaches, fatigue
How is hyperaldosteronism treated?
depends on type:
- aldosterone producing adenomas removed surgically
- spironolactone is mineralcorticoid receptor antagonist
How is cortisol transported in the blood?
bound to transcortin
what effects does cortisol have on the body?
- increase protein breakdown
- incease gluconeogenesis in liver
- increase fat break down in arms and legs (redistributes to abdomen and dorso- cervical fat pad
- supresses immune and inflammatory response (inhibits macrophages and mast cell degranulation)
- resists stress (increases glucose supply, raise blood pressure by making vessels more sensitive to vasoconstriction)
- inihibits insulin induced GLUT4 translocation
What is the name for chronic excess cortisol
cushing’s syndrome
What can cause cushings syndrome?
- prescribed glucocorticoids
- benign pituitary adenoma secreting ATCH (cushings disease)
- excess cortisol from adrenal tumour (adrenal cushings)
- non- pituitary- adrenal tumours producing ATCH or rarely CRH eg small cell lung cancers
How can you differentiate between cushings disease, adrenal cushings and non pituitary- adrenal tumours producing ACTH?
- adrenal tumours producing cortisol (adrenal cushings) will lead to high cortisol levels but low ACTH
- Cushings disease will have high cortisol and ACTH but the ACTH will supress on a supression test (as it is from pituitary cells so has receptors to respond to neg feed back, but this response will be less than normal)
- non-pituitary- adrenal tumours producing ACTH will not react to supression test so ACTH and cortisol will always be high l
What are signs and symptoms of cushings disease?
- plethoric moon shaped face
- buffalo hump (fat on back of neck)
- abdominal obesity
- purple striae
- acute weight gain
- hyperglyaemia
- hypertension
- early stages sometimes present with easy bruising and bones breaking easily
When are steroid drugs such as prednisolone used?
- treatment of inflammatory disorders:
- asthma
- inflammatory bowel disease
- rheumatoid arthirits
- other auto immune conditions
- supress immune response after organ transplant
What are side effects of steroid drugs?
- hypertension
- weight gain
- insomnia (cortisol circadian rythm)
- headaches
- brusing
- achne
What is important about someone taking steroid drugs?
Their dose must be reduce slowly, the course cannot be stopped abruptly.
Why is it that those with cushings disease often have high Na+, low K+, hypertension and urea + creatinine mildly high?
- mildly high urea and creatine it due to more muscle proteolysis due to more cortisol
- high Na+ and low k+ is because cortisol has a similar structure to aldosterone so it will increase transcription of Na/k pump in the nephrons when its levels are very high
- leads to more Na in and more K excreted, as well as increasing BP
What is the name for chronic adrenal insufficiency?
addisons disease
What is most common cause now of addisons disease?
autoimmune (rarer causes inc. TB, fungal infections, adrenal cancer or haemorrhage)
What are signs and symptoms of addisons disease?
- postural hypotension
- hyperpigmentation
- weightloss
- anorexia
- lethargy
- hypoglycaemia
- normal Na+, high k+
- changes to body hair distribution
Why does hyperpigmentation occur in addisons?
- less cortisol
- means more POMC being degraded into ACTH
- ACTH breaks down into a- MSH which causes increased melanin synthesis
- ACTH itself can also activate melanocortin receptors on melanocytes to contribute to hyperpigmentation
Describe an addisonians crisis, why do they occur?
- nausia, vomiting, pyrexia, hypotension, vascular collapse (they get realllly unwell)
- due to severe stress, low salt, infection, trauma, cold, over exertion or abrupt steroid drug withdrawal
- as this is when cortisol levels need to be higher but they cant be
How is an addisonians crisis treated?
- find underlying cause
- hydrocortison/ cortisol
- fluids
Why is urea often high in addisons?
- low blood volume= low glomerular filtration rate
how is androgen release regulated?
partially by ACTH and CRH
What happens to DHEA and what is its function?
- its converted to testosterone in testis which promote puberty and pubic hair growth
- after puberty almost all testosterone is produced by testis, so adrenal release becomes insignificant
Where do osteogens come from before and after menopause?
before: ovaries, other tissues, adrenal glands
after: adrenal glands only (a precursor is made by adrenal glands, other tissues convert it)
How is it that 80% hormone produced by chromaffin cells is adrenaline and 20% noradrenaline
- 20% cells lack N- methyl transferase to convert noradrenaline to adrenaline
Describe the pathway in adrenaline synthesis
- starts with tyrosine
- then levodopa
- then dopamine
- then noradrenaline
- then adrenaline
What type of adrenoreceptors found in heart and what in lungs?
B2 in lungs
B1 in heart
(1 heart, 2 lungs)
What is Pheochromocytoma?
A tumour of the chromaffin cells leading to excess catecholamine release
What are the characteristics of a pheochromocytoma?
- severe hypertension
- headaches
- palpatations
- deaphoesis (increase sweating)
- anxiety
- weightloss
- elevated blood glucose
What is congenital adrenal hyperplasia and what is its cause?
- genetic condition leading to deficiency in 21- hydroxylase
- leads to decreased cortisol and aldosterone production
- but increases androgen production (same pathway a backs up and goes down differnt route)
- so called because low cortisol= high ACTH, which stimulates adrenal glands and causes hyperplasia
What does congenital adrenal hyperplasia present with?
= genital abiguity in female infants
- salt wastin crises (high rate of loss of sodium in urine as no aldosterone)
What tests can be performed for diagnosis of adrenocortical diseases?
- plasma cortisol at differnt times of day (should decrease at midnight and be highest at 8am)
- 24hr urinary excretion of cortisol and its breakdown products
- ACTH stimulation tests (give synthetic ACTH- synacthen and cortisol should increase)
- dexmethasone surpression tests (dexmethasone is synthetic steroid which should decrease ACTH and cortisol)
describe the release of ACTH throughout the day
- released in pulses that follow circadian rythm
- more pulses in early morning
- fewest late evening
