Adrenal Gland Flashcards
Describe where adrenal glands are situated and how they are peritonised
Situated on superior pole of kidney
Retroperitoneal
Describe the venous drainage of the R adrenal v L adrenal
Left adrenal vein drains into left renal vein Right adrenal (usually) drains directly into IVC
What 2 quite separate endocrine glands is the adrenal gland split into?
Adrenal Medulla (~25%) Adrenal Cortex (~75%)
What is the adrenal medulla?
Modified sympathetic ganglion derived from neural crest tissue (neuro)
What does the adrenal medulla secrete?
CATECHOLAMINES mainly epinephrine (adrenaline), also norepinephrine + dopamine
What is the adrenal cortex?
True endocrine gland derived from mesoderm (endo)
What does adrenal cortex secrete?
3 classes of STEROID hormones
What are the 3 classes of steroid hormones secreted by the adrenal cortex?
- Mineralocorticoids e.g. aldosterone
- Glucocorticoids e.g. cortisol
- Sex steroids e.g. testosterone
Both parts of adrenal gland play a role in the body’s response to what?
Stress
What 2 hormones secreted by the adrenal cortex are essential for survival?
Aldosterone
Cortisol
How are the cortex and medulla arranged with respect to each other?
Cortex surrounds medulla
How is the cortex arranged for its function?
in 3 concentric zones which produce different hormones
What are the 3 zones of the adrenal cortex?
Zone glomerulosa
Zona fasciculata
Zona reticularis
What hormones do each of the zones produce?
ZG - aldosterone
ZF - glucocorticoids
ZR - sex hormones
What type of hormones does the adrenal gland produce in general?
Steroid
Although all adrenal gland hormones are steroid, how are different end products produced from diff zones?
Different enzymes are found in different zones
What are the 2 main products of the adrenal cortex?
Cortisol
Aldosterone
What is DHEA (dehydroepiandrosterone)?
Pre-hormone of testosterone and oestrogen - marked decline with age
In the pathway for synthesis of which hormones is 21-hydroxylase enzyme found?
Aldosterone (from corticosterone)
Cortisol
What are defects in 21-hydroxylase enzyme a common cause of?
Congenital adrenal hyperplasia
What does congenital adrenal hyperplasia result in?
Deficiency of aldosterone and cortisol and associated disruption of salt and glucose balance
What happens to androgen biosynthesis in congenital adrenal hyperplasia?
Unaffected; accumulating steroid precursors are channelled into excessive adrenal androgen production
How do babies with CAH present?
Malformed/ambiguous genitalia due to huge excess of sex steroids and underexposure of glucocorticoids
Leaves them incredibly ill in a matter of days - need aldosterone for BP etc
Describe the hypothalamic-pituitary-adrenal pathway
>Hypothalamus >CRH (corticotropin-releasing hormone) >Anterior pituiary > ACTH (adrenocorticotropic hormone) >Adrenal cortex >Cortisol >Target tissue >Response
What is the short loop feedback in this pathway?
ACTH on CRH
What is the long loop feedback in this pathway?
Cortisol on CRH
Why does a deficit of 21-hydroxylase cause adrenal hyperplasia (4 steps)?
- Lack of 21-hydroxylase inhibits synthesis of cortisol
- This removes neg feedback on ACTH + CRH
- Increased ACTH secretion is responsible for enlargement of adrenal glands
- Neg feedback of ACTH on CRH synthesis remains
Steroid yeah, but what specific type of hormone is cortisol?
Glucocorticoid
What does the name glucocorticoid suggest?
it influences glucose metabolism
How is ~95% of plasma cortisol found?
Bound to a carrier protein (cortisol binding globulin (CBG))
Which cells have cytoplasmic glucocorticoid receptors?
ALL nucleated cells
Describe the mechanism of steroid hormone function in the cell
Unbound hormone enters cell and binds to cytoplasmic receptor
Hormone receptor complex migrates to nucleus, binding to DNA via a hormone-response element to alter gene expression
Activated genes create new mRNA that moves back to cytoplasma
Translation produces new proteins for cell processes
Do steroid hormones only bind to cytoplasmic receptors?
No; some can bind to cell surface receptors to produce rapid responses
What characteristic pattern do plasma levels of cortisol show?
A marked circadian rhythm; peak is 6-9am, nadir is midnight; other fluctuations are due to effects of other stressful stimuli
Cortisol as a glucocorticoid is crucial for what?
Helping to protect brain from hypoglycaemia
What action does cortisol have on glucagon?
Permissive
vital as glucagon alone is inadequate
What 4 things does cortisol influence to impact glucose metabolism?
- Gluconeogenesis
- Proteolysis
- Lipolysis
- Decreases insulin sensitivity of muscles + adipose tissue
How does cortisol impact gluconeogenesis?
Stimulates formation of gluconeogenic enzymes in liver thus enhancing gluconeogenesis + glucose production
How does cortisol impact proteolysis?
Stimulates breakdown of muscle protein to provide gluconeogenic substrates for liver
How does cortisol impact lipolysis?
Stimulates lipolysis in adipose tissue which increases FFA in plasma creating alt fuel for protection of BG while also creating glycerol substrate for gluconeogenesis
Cortisol acts to oppose insulin in these glucose counter-regulatory effects and so what does this mean about glucose?
It is diabetogenic
How are the effects cortisol different from GH?
Cortisol is catabolic to proteins
Give 4 additional actions of cortisol (non-glucocorticoid)
- Negative effect on Ca2+ balance
- Impairment of mood and cognition
- Permissive effects on norepinephrine
- Suppression of the immune system
How does cortisol exhibit a negative effect on Ca2+ balance?
Decreases absorption from gut
Increases excretion at kidney
(also increase bone resorption - osteoporosis)
What symptoms does cortisol’s permissive effects on norepinephrine present as in Cushings?
Hypertension
How does supperession of immune system by cortisol occur?
Reduces circulating lymphocyte count
Reduces antibody formation
Inhibits inflammatory response - this can be useul clinically (asthma, UC, transplant)
Steriod, but what specific class of hormone is aldosterone?
Mineralocorticoid
Describe the action of aldosterone as a mineralocorticoid?
Acts on the distal tubule of the kidney to determine the levels of minerals reabsorbed/excreted
How does aldosterone determine mineral levels?
Increases resabsorption of Na+ ions and promotes excretion of K+ ions
How is secretion of aldosterone by the adrenal cortex controlled?
Renin-angiotensin-aldosterone pathway (RAAS)
Describe the end effects of increased aldosterone
Stimulates Na+ (and H2O) retention + K+ depletion = increased blood vol = increased BP
Describe the end effects of decreased aldosterone
Na+ (and H2O) loss and increased plasma K+ = decreased blood vol = decreased BP
2 causes of hypersecretion of cortisol
Cushing’s syndrome/disease
Iatrogenic (too much cortisol administration)
Difference between Cushings syndrome and Cushings disease?
Syndrome - tumour in adrenal cortex
Disease - tumour in pituitary gland (most common)
Give a cause of hyposecretion of cortisol
Addisons disease
What is Addisons?
Hyposecretion of all adrenal steroid hormones
Due to autoimmune destruction of adrenal cortex
Some signs of Cushings?
Fat deposits at base of neck, back, trunk, around face
Wasting of extremities
(interest) Why is there an increasing interest in CRH and ACTH?
May be a key link in how mental state affects immune system
Alcohol, caffeine and lack of sleep all “disinhibit” the Hypothalamo-Pituitary-Adrenal Axis (HPA)
Subsequent elevation of cortisol levels turn down immune system
Do post-ganglionic fibres in adrenal medulla have axons?
No, they release neurohormones (adrenaline) directly into blood
What is a pheochromocytoma?
Rare neuroendocrine tumour found in the adrenal medulla which results in XS catecholamines
Why is care required when withdrawing glucocorticoid treatment?
Enhanced negative feedback effects of exogenous cortisol
What is the risk of withdrawing glucocorticoid treatment too fast?
Loss of trophic action of ACTH on adrenal gland causing atrophy of gland and risk of adrenal insufficiency
What are some side effects of glucocorticoid therapy?
Loss of percutaneous fat stores = thinning skin
Increased severity and frequency of infection
Muscle wastage
(look at diagram)
