8 - Adrenals and Corticosteroids

Question 1

Describe the difference in the blood concentrations of cortisol and aldosterone.

Answer 1

The concentration of cortisol is 1000 times greater than the concentration of aldosterone.

Question 2

What is the arrangement of the juxta-glomerular apparatus in the kidneys?

Answer 2

• juxta-glomerular cells in contact with afferent arteriole

- macula densa cells next to juxta-glomerular cells

Question 3

What are 3 causes of renin release?

Answer 3

• decreased renal perfusion pressure
• increased renal sympathetic activity
• decreased sodium concentration at top of loop of Henle

Question 4

What is the anatomy of the adrenal glands?

Answer 4

• left adrenal vein drains into renal vein
• right adrenal vein drains into IVC
• both adrenals have many arteries but 1 vein
• embedded on superior pole of each kidney
• have their own capsules

Question 5

What is the cross-sectional anatomy of an adrenal gland?

Answer 5

• adrenal medulla: centre of adrenal gland (contains chromaffin cells)
• cortex: outer part of adrenal gland

Question 6

What are the regions of the adrenal cortex and what hormones do they produce?

Answer 6

• zona glomerulosa (aldosterone)
• zona fasciculata (cortisol and glucocorticoid)
• zona reticularis (androgens and oestrogens)

Question 7

What is the blood flow to the adrenals?

Answer 7

• to cortex from arteries that feed outside gland
• passes into zones through cells
• some vessels travel through cortex to get to adrenal medulla

Question 8

What hormones are produced in the medulla of the adrenals and in what percentages?

Answer 8

• catecholamines
• adrenaline (80%)
• noradrenaline (20%)
• dopamine (small amounts)

Question 9

Which hormone groups are produced in the different regions of the adrenal cortex

Answer 9

• zona glomerulosa: mineralocorticoids

- zona fascicularis and zona reticularis: glucocorticoids and sex steroids

Question 10

What are the features of adrenal corticosteroid hormone synthesis?

Answer 10

• cholesterol converted to prenenolone in mitochondria
• pregnenolone precursor to aldosterone production
• androgens produced in adrenal cortex weaker than those made in testes
• androgens are precursors of oestrogens

Question 11

What is androstenesione converted into in the adrenals?

Answer 11

• testosterone

- dihydrotestosterone

Question 12

Which enzymes are used to convert pregnenolone into testosterone and cortisol?

Answer 12

• testosterone: 17-β hydroxysteroid

- cortisol: 21-hydroxylase

Question 13

How are corticosteroids transported in the blood?

Answer 13

• can be taken up by non-target cells

- majority bound to plasma proteins to prevent movement out of blood

Question 14

How does cortisol travel in the blood?

Answer 14

• 80% bound to corticosteroid binding protein (CBG)
• 10% bound to albumin
• 10% unbound
• higher conc. in morning to compared to evening (nmol/l)

Question 15

How does aldosterone travel in the blood?

Answer 15

• 15% bound to corticosteroid binding protein (CBG)
• 45% bound to albumin
• 40% unbound
• conc. variable throughout day (pmol/l)

Question 16

What is the mechanism of action of cortisol?

Answer 16

• binds to glucocorticoid receptors and aldosterone receptors
• when bound to aldosterone receptor, 11b-hydroxysteroid dehydrogenase 2 converts it to cortisone (inactive)

Question 17

What is the mechanism of action of aldosterone?

Answer 17

• can only bind to aldosterone receptors
• stimulates Na+ reabsorption and K+ and H+ secretion in DCT and CD
• increases water retention and BP

Question 18

How does aldosterone stimulate Na+ reabsorption?

Answer 18

• binds to intracellular receptors after passing through cell membranes
• hormone-receptor complex moves to nucleus and attaches to DNA
• particular gene switched on
• aldosterone stimulates synthesis of ion channels (Na+ channels in apical membrane)

Question 19

What are the functions of cortisol?

Answer 19

• stimulates gluconeogenesis and glycolysis in liver
• increases lipolysis (fat metabolism)
• upregulates serotonin 5HT 1A receptors (promotes granule cell division and forms memory)
• anti-inflammatory/immunosuppressive
• decreases glucose uptake by increasing plasma glucose

Question 20

How is aldosterone secreted?

Answer 20

• decreased renal perfusion pressure in afferent arteriole increases renal sympathetic activity in glomerulus
• renin released from juxtaglomerular cells of kidney
• decreased Na+ load at top of loop of Henle causes renin release
• renin breaks down angiotensinogen to angiotensin i (in liver)
• ACE breaks down angiotensin i to angiotensin ii (in kidney)
• angiotensin ii causes vasoconstriction
• aldosterone produced (also increased by corticotrophin)

Question 21

What is the hypothalamo-pituitary-adrenal axis?

Answer 21

• corticotrophs in pituitary controlled by hypothalamic hormones (corticotrophin-releasing hormone)
• cortisol has negative feedback effects to pituitary and indirectly to hypothalamus
• ACTH has negative feedback loop to hypothalamus