The Adrenal Gland Flashcards
Where are adrenal glands located?
The superior pole of the kidney’s in the retro-peritoneal space
How much do the adrenal glands weigh?
Each weigh’s roughly 4g in adults
Where do the adrenal veins drain?
Left adrenal vein into the left renal vein
Right adrenal vein into the IVC
How is the adrenal gland similar to the pituitary gland?
Has two separate glands rolled into one - the adrenal cortex and adrenal medulla
How much of the adrenal gland is the medulla?
25%
What is the medulla made/derived from?
A modified sympathetic ganglion derived from neural crest tissue
What does the medulla secrete?
Catecholamines - mainly adrenaline, NA and dopamine
What does the cortex secrete?
3 classes of steroid hormones
Mineralcorticoids = aldosterone
Glucocorticoids = cortisol
Sex steroids = testosterone
How much of the adrenal gland does the cortex make up? What is it derived from?
75%
A true endocrine gland derived from the mesoderm
What does aldosterone do?
Regulation of Na and K
What does cortisol o?
Involved in maintaining plasma glucose
Do these hormones play a role in stress response?
Yes
Structure of the adrenal gland?
A triangular cortex the surrounding an inner triangular medulla
What are the 3 zones from top to bottom of the cortex?
Zona glomerulosa = aldosterone
Zona fasciculata = glucocorticoids
Zona reticularis = sex hormones
If all steroid hormones are made from cholesterol how do the 3 zones make different hormones?
Different enzymes = different end products
What is DHEA?
A pre-hormone of testosterone and oestrogen
Marked decline with age
Outline the basic synthetic pathway for aldosterone.
Cholesterol –> progesterone –> corticosterone –> aldosterone
21-hydroxylase is crucial to the Progesterone to corticosterone reaction
What do defects in 21-hydroxylase cause?
Congenital adrenal hyperplasia which results in deficiencies of aldosterone and cortisol and the associated disruption of salt and glucose balance
This also leads to overproduction of androgens (sex hormones) because steroid precursors begin to accumulate and are funneled into this pathway
Describe the pathway (hypothalamus to adrenal glands) for cortisol release.
Also describe the feedback loops present.
Hypothalamus releases CRH onto the AP gland which releases ACTH onto the cortex leading to release of Cortisol
Short loop = Increase of ACTH inhibits release of CRH
Long loop = increased cortisol inhibits CRH release
Why does a deficit in 21-hydroxylase results in adrenal hyperplasia?
Cortisol synthesis stops removing the long neg. feedback loop which increases CRH and ACTH secretion
Increased levels of ACTH causes hyperplasia of the adrenal gland
The short feedback loop of increased ACTH inhibiting CRH still in place
What class of hormone is cortisol?
A glucocorticoid - meaning it influences glucose metabolism
What % of cortisol in plasma is bound to a carrier - what is the carrier called?
~95% is bound to cortisol-binding-globulin (CBG)
What type of cells have cytoplasmic glucocorticoid receptors?
ALL nucleated cells
What happens to the cytoplasmic receptor once cortisol binds?
It migrates to the nucleus and binds to DNA top alter gene expression
Do all steroid hormones bind within the cell?
No - some bind to a receptor on the membrane that uses 2nd messengers to create more rapid responses
Is the plasma levels of cortisol erratic or constant?
Has a relatively characteristic pattern it follows
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
When is the peak of cortisol usually?
6am to 9am
When is the lowest levels?
Midnight
What causes the fluctuations throughout the day of cortisol?
Stimuli related to tress
Is cortisol needed for life?
Yes, removal of adrenal glands in animals = death in a few weeks
Why is cortisol so essential?
Loss of cortisol deprives you of the ability to regulate blood glucose levels in times of stress
How does cortisol affect glucagon?
Has a permissive action of glucagon which is vital as without it, glucagon alone can’t protect the brain from hypoglycaemia
What else does cortisol act on?
Gluconeogenesis - increases it by stimulating formation of gluconeogenic enzymes
Proteolysis - stim’s breakdown of muscle proteins to provide gluconeogenic substrates
Lipolysis - making FFAs as a back up fuel source while also making glyceol for gluconeogenesis
Decreases insulin sensitivity of muscles and adipose tissue
So does cortisol oppose or help insulins actions?
Opposes
What other effects does cortisol have that is not glucose related?
Negative effect on Ca2+ balance - causes reduction by excess secretion
Impairments on mood and cognition
Permissive effects on NA
Suppression of the immune system
What is a consequence of cortisol having a permissive effect on NA?
Causes vasoconstriction - so in diseases such as cushing’s it can cause hypertension
Equally low levels of cortisol = hypotension
What is cushing’s disease?
Hypercortisolaemia
How does cortisol suppress the immune system?
Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response.
Why would cortisol inhibiting an inflammatory response be useful clinically?
Can be used to treat disease like asthma
What are some main side effects of glucocorticoid therapy?
Increased severity and risk of infections
Muscle wastage due to gluconeogenesis and proteolysis
Loss of percutaneous fat stores due to lipolysis gives appearance of “thinning skin” making it more fragile.
Where does aldosterone act?
On the distal tubule of the kidney
What does aldosterone do?
Increases reabsorption of Na+
Promotes excretion of K+
What controls the secretion of aldosterone in the kidneys?
The Renin-angiotensin-aldosterone-system (RAAS)
Effect of increased aldosterone on CV system?
Stimulates sodium and water retention = increase in blood volume and pressure
Effect of decreased aldosterone on CV system?
Leads to sodium and water excretion and retention of K+ = dimished blood volume and decreased blood pressure
Can you live without aldosterone?
No
What are the different causes of hypersecretion of cortisol and how are they classed?
Which one is most common?
1y hypercortisolism = tumour in the adrenal cortex = Cushing’s syndrome
2y hypercortisolism = tumour in the pituitary gland - Cushing’s Disease (Most common)
Iatrogenic - too much cortisol administered therapeutically
What causes hyposecretion of cortisol?
Addison’s disease - is hyposecretion of all adrenal steroid hormones due to autoimmune destruction of the cortex
Classic symptoms of cushing’s?
Fat face (moon face) and trunk but skinny arms and legs Abdominal striae Buffalo "hump" - fat on back on neck Easy brusing and poor wound healing Muscle weakness
Does stress promote release of CRH and ACTH?
Yes
What can disinhibit the Hypothalamo-Pituitary-Adrenal Axis causing increase in hormone levels?
Alcohol
Caffeine
Lack of sleep
Alcohol in particular depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH
Is the adrenal true endocrine tissue?
No, it’s a modified sympathetic ganglion
How does the adrenal medulla release neurohormones into the blood?
Preganglionic sympathetic fibres terminate on specialised postganglionic cells in the adrenal medulla which release neurohormes directly into the blood
Describe a pathology affecting the adrenal medulla. How is it treated?
Pheochromocytoma -a rare tumour, found in adrenal medulla, which results in excess catecholamines
This increases HR, CO and BP
Is also diabetogenic due to the adrenergic effect on glucose metabolism
Responds well to surgery
What would the levels of CRH, ACTH and Cortisol be in the issue was in the hypothalamus? What sort of hyper-secretion would this cause?
All 3 would be high
Secondary hypersecretion
What would the levels of CRH, ACTH and Cortisol be if the issue was in the pit. gland? What sort of hyper-secretion would this cause?
CRH would be low
ACTH and cortisol would be high
This is because the hypothalamus works fine, and the higher levels of ACTH due to the pit. gland tumour causes a feedback loop inhibiting CRH
2y hypersecretion again
What would the levels of CRH, ACTH and Cortisol be if the issue was in the cortex? What sort of hyper-secretion would this cause?
CRH and ACTH will be low and cortisol will be high - due to feedback loops inhibiting CRH and ACTH but pathology causing increase in cortisol levels
Primary hyper secretion
Why is care taken when withdrawing patients from glucocorticoid therapy?
Therapeutic cortisol enhances the negative feedback loops on hypothalamus and pituitary reducing release of CRH and ACTH.
Loss of trophic action of ACTH on adrenal gland can cause atrophy of gland - if withdrawel is too fast the cortex won’t be able to make cortisol instantly. Need to wean patient off
