Adrenal Physiology

Question 1

The adrenal cortex is involved in ______ hormone synthesis

Answer 1

Steroid

• cortisol: gluconeogenesis, anti-inflammatory (regulated by HPA axis)
• aldosterone: blood volume regulation, secretion of K and resorption of Na from kidney (regulated by RAAS)

Question 2

Adrenal medulla is responsible for synthesizing ________

Answer 2

Catecholamines

- regulation via SNS

Question 3

The zona fasiculata produces _____

Answer 3

• cortisol

- corticosterone

Question 4

The zona glomerulosa produces _______

Answer 4

Aldosterone

Question 5

The zona reticularis produces ________

Answer 5

Androstenedione

Question 6

Corticosteroids

Answer 6

Refers to all hormones made in the adrenal glands

• glucocorticoids (cortisol)
• mineralcorticoids (aldosterone)
• sex steroids (progestogens, androgens, estrogens)

Question 7

Anabolic steroids

Answer 7

• increased protein synthesis
• increased muscle mass
• typically androgens

Question 8

Catabolic steroids

Answer 8

• decreased protein synthesis
• decreased muscle mass
• usually glucocorticoids: cortisol, prednisone

Question 9

Adrenal gland components

Answer 9

• adrenal cortex (80%) –> steroid hormones

- adrenal medulla (20%) –> catecholamine synthesis, SNS regulation

Question 10

Catecholamine synthesis

Answer 10

• released into blood
• fight or flight
• norepinephrine (cat)
• epinephrine (dog, human)
• increase metabolic rate
• increase blood pressure, cardiac contractility, myocardial excitablity

Question 11

Pheochromocytoma

Answer 11

Tumor of adrenal medulla with excess production of catecholamines

Question 12

Cortex components

Answer 12

• glomerulosa (15%)
• fasiculata (75%)
• reticularis (10%)

Question 13

Glomerulosa

Answer 13

• specific enzyme: aldosterone synthase

- product: mineralocorticoids

Question 14

Fasiculata

Answer 14

• specific enzyme: 17alpha-hydroxylase

- product: glucocorticoids, sex hormones

Question 15

Reticularis

Answer 15

• specific enzyme: 17alpha- hydroxylase

- products: glucocorticoids, sex hormones

Question 16

Steroids are degraded in the ______

Answer 16

Liver

• free hormone
• conjugated to glucuronide
• excreted thru urine, bile
• inhibited if diseased

Question 17

Steroids are bound to proteins 94%, but only the ________ is active

Answer 17

Free hormone

Question 18

Cortisol metabolism

Answer 18

• corticosteroid-binding globulin (CBG)
• albumin
• T1/2 < 2 hrs

Question 19

Aldosterone metabolism

Answer 19

• albumin
• slightly bound
• T1/2 is 20 minutes

Question 20

Steroidal mechanism of action

Answer 20

Free hormone diffuses into cell (lipophilic) –> binds cytoplasmic receptor –> translocates to nucleus, binds DNA –> directs transcription (proteins)

Question 21

What are the cellular functions of cortisol?

Answer 21

• catabolic: gluconeogenesis, anti-insulin, protein
• anti-inflammatory
• anti-stress
• receptors in most cells*

Question 22

Catabolic effects of cortisol on carbohydrates

Answer 22

• stimulates hepatic gluconeogenesis
• inhibits effects of insulin
• fight or flight
• protects from hypoglycemia

Question 23

Catabolic effects of cortisol on lipids

Answer 23

• mobilizes fatty acids

- redistribution

Question 24

Catabolic effects of cortisol on proteins

Answer 24

• inhibits cellular uptake of amino acids
• stimulates gluconeogenesis
• muscle breakdown
• skin, CT, bone

Question 25

Anti-inflammatory/immunosuppressive function of cortisol

Answer 25

- stabilization of lysosomes - decreases: capillary permeability, margination of WBCs - suppression of T lymphocytes - decreases fever (IL-1) - blocks allergies * give glucocorticoids during anaphylactic shock*

Question 26

3 functions of cortisol

Answer 26

- resistance to stress - stimulation of erythropoiesis - maintenance of vascular tone

Question 27

Functions of cortisol: summary

Answer 27

- gluconeogenesis - protein catabolism - stress resistance - anti inflammatory - immunosuppressive

Question 28

The hypothalamic-pituitary-adrenal axis

Answer 28

``` Hypothalamus - corticotropin releasing hormone - physical, emotional, chemical stress Anterior pituitary - adrenocorticotropic hormone Adrenal gland - cortisol ```

Question 29

Adrenocorticotropic hormone

Answer 29

``` Episodic secretion (concentration varies) - precursor: pro-opiomelanocortin (POMC) ```

Question 30

ACTH mechanism of action

Answer 30

Increase free cholesterol --> conversion of cholesterol to pregnenolone --> major action of ACTH --> rate-limiting step in cortisol synthesis - trophic effect

Question 31

Increase stress in a normal dog results in:

Answer 31

Hypothalamus increases CRH --> pituitary increases ACTH --> adrenal increases cortisol

Question 32

Feedback inhibition

Answer 32

- increased ACTH = decreased CRH - increased cortisol = decrease CRH - increased cortisol = decreased ACTH

Question 33

Would you measure cortisol to determine if a dog has hypoadrenocorticism?

Answer 33

No, ACTH is secreted episodically so a normal dog could have a low cortisol

Question 34

What happens if you give dexamethasone to a healthy dog?

Answer 34

Dex will suppress cortisol production, so the cortisol levels will be less than the level collected before the injection

Question 35

Pituitary tumor

Answer 35

Will cause: - increased ACTH - bilaterally increase adrenals - increase cortisol

Question 36

________ is the most important endogenous mineralocorticoid

Answer 36

Aldosterone - 90% of body's mineralocorticoid effects - some glucocorticoids have a small amount of mineralocorticoid effect

Question 37

Aldosterone release is stimulated by

Answer 37

- decreased blood volume, decreased sodium | - increased potassium

Question 38

Primary functions of aldosterone

Answer 38

- increased Na, Cl and water resorption | - increased K and H excretion

Question 39

Aldosterone site of action

Answer 39

Principal cells of distal tubules and collecting ducts - increase activity of basolateral Na/K ATPase - increase transcription of luminal Na channels

Question 40

Renin-angiotensin-aldosterone system (RAAS)

Answer 40

``` Renin - released from afferent arteriole - response to hypovolemia Angiotensin - renin converts angiotensingogen to AT - AT converted to AT2 by ACE in the lungs - AT2 stimulates aldosterone synthesis ```

Question 41

Aldosterone regulation

Answer 41

Hypovolemia --> increase renin --> stimulates conversion of angiotensinogen to angiotensin --> AG2 by angtiotensin converting enzyme --> AT2 stimulates production of aldosterone