Adrenal Gland Flashcards
Describe the location of the L and R adrenal glands
embedded on superior pole of kidneys with own capsule
L adrenal vein drains into renal vein
R adrenal vein drains into IVC
Describe a cross section of the adrenal gland
adrenal medulla - centre of adrenal gland
outer region - cortex (consists of 3 zones)
- zona reticularis
- zona fasciculata
- zona glomerulosa
What is the structure of each of the cortical zones?
Blood flow to zones by passing through cells / vessels pass through cortex to medulla
reticularis - no pattern
fasciculata - cells line up as strings
What hormones are produced by the adrenal medulla?
catecholamines by chromaffin cells
adrenaline 80%
noradrenaline 20%
dopamine in small amounts
What are chromaffin cells?
found in the adrenal medulla
= specialised post ganglionic nerve fibres
- cells innervated by preganglionic fibres that release substances as hormones into the circulation
- sympathetic innervation
What hormones are produced by the cortex?
corticosteroids
mineralocorticoids C21 - aldosterone (by zona glomerulosa)
zona fasciculata/reticularis
glucocorticoids C21 - cortisol
sex steroids - androgens C19, oestrogens C18
What are all steroid hormones derived from?
cholesterol
What is the nucleus of cholesterol?
cyclopentanoperhydrophenanthrene
How are cortical hormones made?
steroid hormones are not stored as they are lipophilic and easily pass through the membrane
- progesterone is the precursor for aldosterone
- androgens are weak and potentiated in the testes
- androstenedione can be converted to testosterone and dihydrotestosterone
- androgens are precursors to oestrogens
How are corticosteroids transported in the blood?
bound to plasma proteins to prevent uptake by nontarget cells
cortisol
- 75% to corticosteroid binding globulin CBG/transcortin
- 15% to albumin
- 10% unbound and BIOACTIVE
aldosterone
- 45% bound to albumin
- 15% bound to CBG
- 40% unbound
Describe changes in cortisol and aldosterone [] in circulation throughout the day
Cortisol am (140-690nmol/l), pm (80-330nmol/l) diurnal variation Aldosterone upright (140-560pmol/l) Units show 1000 fold difference between cortisol and aldosterone (much more CORTISOL)
- cortisol levels change depending on time of day
- released in pulses
- aldosterone not controlled by pituitary so time of day irrelevant but position is important as aldosterone controls fluid and balance
What are the general effects of aldosterone?
stimulates Na reabsorption into blood in DCT and CD
stimulates K/H secretion in DCT and CD into tubule lumen (affect blood pH)
What is the mechanism of aldosterone action?
- pass through membrane, bind to intracellular receptors
- hormone receptor complex moves to nucleus and attaches to DNA, switch on certain genes (TF)
- proteins (pumps/enzymes) produced
- proteins may stimulate ATPase pump on basolateral membrane to pump Na into blood
- stimulates synthesis of Na ion channels in apical membrane
Describe how the juxtaglomerular apparatus controls aldosterone
macula densa (cells lining ascending limb of loop of Henle) touch (juxtaglomerular cells) cells lining afferent arteriole
- they respond to changes in Na ion [], renal perfusion pressure, renal sympathetic activity
- juxtaglomerular cells produce enzyme RENIN that is important in aldosterone production
- aldosterone stimulates Na reabsorption to increase plasma osmolality
- stimulates ADH release to increase water reabsorption in CD and expand extracellular fluid volume
- if maintained high fluid volume –> hypertension
What causes renin release?
- decreased renal perfusion pressure (decrease arteriole blood pressure)
- increased renal sympathetic activity to juxta-glomerular cells after drop in BP
- decreased Na load to top of loop of Henle - activate JGA and release renin
Describe the RAAS (process whereby renin stimulates release of aldosterone)
- liver produces angiotensinogen that is broken down by renin to angiotensin I
- ACE converts this to angiotensin II
- Angiotensin II
- stimulates zona glomerulosa to produce aldosterone
- vasoconstriction
What other factors affect aldosterone production?
corticotrophin has a permissive effect by enhancing RAAS
angiotensin regulates ions so if blood Na[] falls it directly affects aldosterone production (increase) to increase Na reabsorption
increase K[] stimulates aldosterone production leading to increase secretion of potassium
What are the metabolic effects of cortisol?
stimulate peripheral protein catabolism (excess in Cushings causes thin arms and legs due to muscle loss)
hepatic gluconeogenesis fat metabolism enhance effects of glucagon/catecholamines stimulate glycogenolysis tissue less responsive to insulin ALL INCREASE BLOOD GLUCOSE []
also affects mineralocorticoids, renal, CVS, bone, CNS, growth
What are the 3 effects of large pharmacological amounts of cortisol?
antiinflammatory action
immunosupressive action
antiallergic action
decrease production of prostaglandin, leukotrienes, histamines, interleukins, movements of leukocytes
Describe corticosteroid receptors (aldosterone and cortisol)
- aldosterone binds almost always to mineralocorticoid receptors (affects salt and water balance)
cortisol bind to GCR and MR receptors equally - 1000x greater cortisol [] in blood than aldosterone but cortisol not always binding with MR as kidneys produce 11b-hydroxysteroid dehydrogenase 2 enzyme that converts bioactive cortisol to inactive cortisone so it cannot interact with MC receptors
What is the mechanism of action of cortisol?
genomic effect binding to intracellular receptor
- cell produces annexin 1
- this leaves cell to have autocrine effect and bind to own annexin 1 receptor
- binding affects phospholipase enzyme that causes membrane phospholipids to produce arachidonic acid (prostaglandin precursor)
- cortisol blocks arachidonic acid and prostaglandin production
How is cortisol production controlled?
- corticotrophs under control of hypothalamic neurones
- cortisol has negative feedback directly to pituitary and indirectly to hypothalamus
- ACTH is an autonegative feedback loop to hypothalamus
What is the circadian rhythm for cortisol?
originates from the biological clock in the suprachiasmatic nucleus
What is DHEA?
- weak androgen
- precursor for androgens and oestrogens, converted to active hormone in target cells
- peak serum levels at 20-30yrs and decrease steadily with age
- in post menopausal women important as precursor for oestrogen/androgen synthesis by target tissue in the absence of ovarian steroids
