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Flashcards in Adrenal Deck (55)
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1

Location of Adrenal gland

The adrenal (or suprarenal) gland sits on top of the
kidney (ad – near, supra – above, renal –kidney).

2

Divisions of Adrenal Gland

Zona glomerulosa(cortex)
Zona fasciculata(cortex)
Zona reticularis(cortex)
Adrenal Medulla

3

What does zona fasiciculata produce and what enzyme does it lack

glucocorticoid cortisol
lacks aldosterone synthase

4

What does zona reticularis produce and what enzyme does it lack

lacks aldosterone synthase
adrenal androgens
androstenedione
dehydroepiandrosterone acetate (DHEA)

5

What is Acth derived from

ACTH derived from pro-opiomelanocortin
(POMC)

6

What other products do you get from POMC breakdown

g-lipotrophin (g-LPH),b-MSH ACTH main ones

7

REGULATION OF SYNTHESIS of cortisol brief outline involving axis

hypothalamus releases CRH, causes anterior pituitary corticotrophs to release acth, causes cortex to synthesis and release cortisol. negatuve feedback from cortisol to hypothalamus and pituitary

8

What molecule are all steroid hormones derived from

Chlesterol

9

What receptor does ACTH act on

ACTH acts on a G-protein coupled receptor
(melanocortin 2 receptor, MC2R) to activate adenyl
cyclase which leads to an increase in cAMp level and activation of PKA

10

What enzymes are involved in synthesis of cortisol in zona fascicuclata

cholesteryl ester hydrolase (CEH)

cholesterol 20,22-hydroxylase also referred to as
desmolase

11

What enzyme is the rate limiting step in cortisol synthesis

desmolase

12

Describe action of the enzymes in synthesis of cortisol

All steroid hormones are derived from cholesterol.
ACTH acts on a G-protein coupled receptor
(melanocortin 2 receptor, MC2R) to activate adenyl
cyclase which leads to an increase in cAMP levels.
This in turn activates protein kinase A which activates
cholesteryl ester hydrolase (CEH) which liberates
cholesterol from lipid droplets. There is also stimulation
of cholesterol 20,22-hydroxylase also referred to as
desmolase which is the first enzyme in the pathway and
is the rate limiting step. This leads to increased synthesis
of cortisol.

13

Name the five steroid hormones produced by adrenal gland

cortisol, corticosterone, aldosterone, DOC(Deoxycorticosterone), DHEA(Dehydroepiandrosterone)

14

How is cortisol transported in the blood plasma

CBG corticosteroid binding globulin 75% , albumin 15% , free 10%

15

How is aldosterone transported in the blood plasma

free 40%, albumin bound 40% and CBG 20%

16

When steroid hormone binds to cytoplasmic receptor what protein dissociates from receptor

Steroid hormone enters cells by diffusion and binds to
cytoplasmic receptor. This leads to dissociation of Heat
Shock Protein (hsp90) from the receptor.

17

Once steroid hormone has bound to cytoplasmic receptor outline what occurs

The hormone-receptor complex dimerises and is
translocated to nucleus. The complex binds to hormone
responsive element (HRE) on DNA which leads to an
increase in mRNA production and subsequently to
increased protein synthesis.

18

Why is steroid action have a slower effect on the body

The complex binds to hormone
responsive element (HRE) on DNA which leads to an
increase in mRNA production and subsequently to
increased protein synthesis.
Protein sythesis is slow

19

EFFECTS OF GLUCOCORTICOIDS (cortisol) on glucose

decrease glucose uptake
decrease glucose use
increase gluconeogenesis
"hyperglycaemia"

20

EFFECTS OF GLUCOCORTICOIDS (cortisol) on proteins

decrease protein synthesis
increase protein breakdown
"muscle wasting"

21

EFFECTS OF GLUCOCORTICOIDS (cortisol) on calcium

decrease Ca2+ absorption in gut
increase Ca2+ excretion in kidney
decrease activity of osteoblasts
increase activity of osteoclats
"osteoporosis"

22

EFFECTS OF GLUCOCORTICOIDS (cortisol) on inflammatory early phase

anti-inflammatory effects
early phase
reduce redness, heat, pain, swelling

23

EFFECTS OF GLUCOCORTICOIDS (cortisol) on inflammatory late phase

late phase
reduce wound healing, repair, proliferation

24

EFFECTS OF GLUCOCORTICOIDS (cortisol) on immune response

decreases expression of COX2 (cyclo-oxygenase 2)
cytokine production
complement in plasma
nitric oxide (NO) production
histamine release
IgG production

25

How is cortisol action on mineralcorticoid recptors prevented

cortisol has higher affinity for mineralocorticoid
receptor than glucocorticoid receptor
11bHSD
cortisol ------→cortisone
active inactive
11bHSD 11bhydroxysteroid dehydrogenase
11bHSD2 isoform expressed in aldosterone
sensitive tissues
converts cortisol ---→ cortisone
11bHSD1 isoform expressed in liver,adipose,
muscle
converts cortisone ---→ cortisol

26

What causes Cushing syndrome

Cushing syndrome due to
prolonged exposure to
elevated levels of cortisol
or exogenous
glucocorticoid drugs

27

What symptoms associated with cushing syndrome

Osteoporosis
Negative nitrogen
balance
Increased appetite
Obesity
Increased susceptibility to
infection

28

What drugs can be used to treat cushing syndrome and how do they work

Metyrapone
11b hydroxylase inhibitor
• Ketoconazone (withdrawn in Europe)
inhibits steroid biosynthesis
• Pasireotide (somatostatin analogue)
SSTR5 agonist
● Cabergoline (dopamine D2 agonist)
● Mifeprestone
glucocorticoid receptor antagonist
progestogen receptor antagonist

29

What causes Addison disease

Low cortisol- Chronic adrenal insufficiency

30

Symptoms associated with Addisons

Hypotension, weight loss, hyperpigmentation,gastro disturbances