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OSSF II Endocrinology > Adrenal Glands > Flashcards

Adrenal Glands Flashcards

1
Q

List the layers of the adrenal gland in order (out-to-in) and what each produces.

A
  1. Zona glomerulosa (mineralocorticoids)
  2. Zona fasciculata (glucocorticoids)
  3. Zona reticularis (androgens)
  4. Adrenal medulla (catecholamines)
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2
Q

Which two factors stimulate aldosterone release from the zone glomerulosa?

A
  1. Hyperkalemia

2. Angiotensin 2

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3
Q

Steps in cortisol synthesis

A
  1. ACTH activates adenyl cyclase, which converts ATP (from glycolysis) to cAMP
  2. cAMP activates Protein Kinase A
  3. Protein Kinase A promotes cholesterol ester -> cholesterol
  4. Desmolase converts cholesterol to pregnenolone
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4
Q

What is the rate-limiting step in adrenal steroid biosynthesis?

A

Cholesterol -> pregnenolone (side chain cleavage, mediated by desmolase)

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5
Q

Describe species differences in cortisol v corticosterone

A

Cats, sheep, and primates = Cortisol > Corticostreone

Dogs = equal amounts of each

Birds, reptiles, amphibians, mice, and rats = Corticosterone > cortisol

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6
Q

Which organs convert cortisol to cortisone and which enzyme catalyzes this conversion?

A

Kidney and liver
HSD-2

HSD-1 can restore cortisone to the more potent cortisol

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7
Q

Compare and contrast cortisone and corticosterone

A

Cortisone has weaker glucocorticoid activity than cortisol

Corticosterone has even weaker glucocorticoid activity but has strong mineralocorticoid activity

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8
Q

What transports most of the cortisol in plasma?

A

Transcortin (note that cortisol is inactive when bound; more bound than free in plasma)

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9
Q

Cushing’s vs Addison’s

A 
Cushing's = hi cortisol
Addison's = lo cortisol
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10
Q

Effects of glucocorticoids on liver

A
  1. Stimulates gluconeogenesis
  2. Stimulates hepatic glycogenesis
  3. Increases blood glucose
  4. Increases angiotensinogen, leading to hypertension
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11
Q

Effect of glucocorticoid on adipose

A
  1. Lipolysis (liver then uses FFAs for TG and ketone body synthesis)
  2. Increase hormone-sensitive lipase
  3. Decrease glucose uptake
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12
Q

Effect of glucocorticoid on muscle/bone

A

Catabolic (negative nitrogen balance)

i.e. degrades proteins and inhibits protein synthesis

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13
Q

Glucocortidoids have _____ effects on the liver and _____ effects on muscle, fat, connective tissue, and lymphoid tissue.

A

Anabolic

Catabolic

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14
Q

Effect of glucocorticoid on pituitary

A
  1. Downregulates all 6 products of anterior pituitary and ADH from neurohypophysis
  2. Consequence of decreased TSH is decreased LDL receptors -> increased plasma cholesterol
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15
Q

Synergistic effects of amines (thyroid hormones and catecholamines) and cortisol

A
  1. Thyroxine alone has no effect on adipoctye
  2. Epinephrine alone causes small amount of FFA release
  3. Cortisol + thyroxine + epinephrine = large FFA release
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16
Q

Regulation of lipolysis

A
  1. Catecholamines bind B1-receptor
    a. T4, T3 increase B1- receptor
  2. Binding activates adenyl cyclase
  3. cAMP activates protein kinase
  4. Protein kinase phosphorylates/activates HSL
    a. Glucocorticoids promote HSL synthesis
17
Q

Effect of glucocorticoid on Bone and CT

A
  1. Hypocalcemia
    a. Increased PTH
    b. Decreased osteoblast protein synthesis
    c. Decreased bone mass
  2. Decreased fibroblast activity
    a. Decreased muscle and thin skin
  3. Decrease in Type 1 collagen synthesis contributes to both the decreased bone mass and decreased skin thickness
18
Q

Steps in Prostaglandin and thromboxane synthesis (how glucocorticoids suppress inflammatory response)

A
  1. Phospholipase A2 converts membrane phospholipid to arachidonic acid
    a. Glucocorticoids suppress PLA2
    b. Angiotensin 2 promotes PLA2
  2. COX 1 and 2 convert arachidonate to prostaglandins and thromboxanes
    a. Glucocorticoids inhibit COX-2
    b. NSAIDs inhibit both COXes
19
Q

How do glucocorticoids contribute to ulcers?

A
  1. Decrease prostaglandin production (via PLA2 and COX2 inhibition)
    a. Increase Hcl
    b. Decreases
    HCO3/mucus
  2. Decreased COX2 inhibits repair
20
Q

Effect of glucocorticoid on duodenum

A

Decreased Ca absorption due to blunted Vitamin D

21
Q

How do glucocorticoids contribute to hypertension?

A
  1. Increase Cardiac Output
  2. Decrease endothelium permeability
  3. Increases responsiveness to constrictors (NE and angiotensin 2)
  4. Decreases responsiveness to dilators (prostaglandins and NO)
22
Q

Causes of glucocorticoid excess

A
  1. Pituitary tumor: ACTH -> cortisol [Cushing’s DISEASE]
  2. Adrenocortical tumor: increased cortisol and decrease ACTH [Cushing’s syndrome]
  3. XS glucocorticoid therapy (same as C syndrome)
23
Q

Causes of glucocorticoid deficiency

A
  1. Autoimmune destruction of adrenal cortex/pituitary

2. Treatment w/ adrenal suppressors OR body’s reaction after prolonged glucocorticoid therapy

24
Q

Cushing’s Disease

A

Cortisol: hi
ACTH: hi

25
Q

Cushing’s syndrome

A

Cortisol: hi
ACTH: lo

26
Q

Addison’s disease

A

Cortisol: lo
ACTH: hi

27
Q

Pituitary insufficiency

A

Both ACTH and Cortisol are lo

28
Q

Aldosterone actions

A

Increases blood pressure:
a. Increases salt/water absorption (at expense of potassium)

Angiotensin 2 (stimulates aldosterone release) is a vasoconstrictor

29
Q

Name the four sites of aldosterone action

A
  1. Principal cells of distal tubules (inserts Na/K pump and Na channels)
  2. Salivary and sweat glands
  3. Skeletal muscle
  4. Large intestine
30
Q

Where does conversion of androgen to estrogen take place, and which enzyme catalyzes this conversion?

A

Adipose

Aromatase

31
Q

Steroid fates

A
  1. Androgens -> keto steroids -> sulfates -> urine/bile
  2. Aldosterone and corticosterone -> tetrahydro-derivatives -> glucouronides -> urine/bile
    a. Remember b/c aldosterone and corticosterone both have mineralocorticoid activity
  3. Cortisol/cortisone can go through the keto steroid route, the tetrahedron-derivate route, or directly to sulfates
32
Q

How does aldosterone contribute to ascites?

A

When liver is damaged, albumin production and therefore plasma oncotic pressure decreases

leakage of fluid out of blood vessels triggers RAAS system, which promotes water retention via aldosterone (but this water does not stay in blood vessels and contributes to swelling)

33
Q

Loss of the adrenal cortex is fatal due to the loss of which steroids?

A
  1. Glucocorticoids

2. Mineralcorticoids

OSSF II Endocrinology (11 decks)

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