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Endocrinology > Adrenal Gland > Flashcards

Adrenal Gland Flashcards

1
Q

Describe the location of the L and R adrenal glands

A

embedded on superior pole of kidneys with own capsule
L adrenal vein drains into renal vein
R adrenal vein drains into IVC

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2
Q

Describe a cross section of the adrenal gland

A

adrenal medulla - centre of adrenal gland
outer region - cortex (consists of 3 zones)
- zona reticularis
- zona fasciculata
- zona glomerulosa

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3
Q

What is the structure of each of the cortical zones?

A

Blood flow to zones by passing through cells / vessels pass through cortex to medulla
reticularis - no pattern
fasciculata - cells line up as strings

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4
Q

What hormones are produced by the adrenal medulla?

A

catecholamines by chromaffin cells
adrenaline 80%
noradrenaline 20%
dopamine in small amounts

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5
Q

What are chromaffin cells?

A

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

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6
Q

What hormones are produced by the cortex?

A

corticosteroids
mineralocorticoids C21 - aldosterone (by zona glomerulosa)
zona fasciculata/reticularis
glucocorticoids C21 - cortisol
sex steroids - androgens C19, oestrogens C18

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7
Q

What are all steroid hormones derived from?

A

cholesterol

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8
Q

What is the nucleus of cholesterol?

A

cyclopentanoperhydrophenanthrene

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9
Q

How are cortical hormones made?

A

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
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10
Q

How are corticosteroids transported in the blood?

A

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
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11
Q

Describe changes in cortisol and aldosterone [] in circulation throughout the day

A 
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
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12
Q

What are the general effects of aldosterone?

A

stimulates Na reabsorption into blood in DCT and CD

stimulates K/H secretion in DCT and CD into tubule lumen (affect blood pH)

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13
Q

What is the mechanism of aldosterone action?

A
  • 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
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14
Q

Describe how the juxtaglomerular apparatus controls aldosterone

A

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
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15
Q

What causes renin release?

A
  1. decreased renal perfusion pressure (decrease arteriole blood pressure)
  2. increased renal sympathetic activity to juxta-glomerular cells after drop in BP
  3. decreased Na load to top of loop of Henle - activate JGA and release renin
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16
Q

Describe the RAAS (process whereby renin stimulates release of aldosterone)

A
  1. liver produces angiotensinogen that is broken down by renin to angiotensin I
  2. ACE converts this to angiotensin II
  3. Angiotensin II
    - stimulates zona glomerulosa to produce aldosterone
    - vasoconstriction
17
Q

What other factors affect aldosterone production?

A

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

18
Q

What are the metabolic effects of cortisol?

A

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

19
Q

What are the 3 effects of large pharmacological amounts of cortisol?

A

antiinflammatory action
immunosupressive action
antiallergic action

decrease production of prostaglandin, leukotrienes, histamines, interleukins, movements of leukocytes

20
Q

Describe corticosteroid receptors (aldosterone and cortisol)

A
  • 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
21
Q

What is the mechanism of action of cortisol?

A

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
22
Q

How is cortisol production controlled?

A
  • 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
23
Q

What is the circadian rhythm for cortisol?

A

originates from the biological clock in the suprachiasmatic nucleus

24
Q

What is DHEA?

A
  • 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
25
Q

When is best to measure blood cortisol levels?

A

levels vary with time

take reading when the readings are expected to be highest/lowest

Endocrinology (13 decks)

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