Adrenal Physiology Flashcards
The adrenal cortex is involved in ______ hormone synthesis
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)
Adrenal medulla is responsible for synthesizing ________
Catecholamines
- regulation via SNS
The zona fasiculata produces _____
- cortisol
- corticosterone
The zona glomerulosa produces _______
Aldosterone
The zona reticularis produces ________
Androstenedione
Corticosteroids
Refers to all hormones made in the adrenal glands
- glucocorticoids (cortisol)
- mineralcorticoids (aldosterone)
- sex steroids (progestogens, androgens, estrogens)
Anabolic steroids
- increased protein synthesis
- increased muscle mass
- typically androgens
Catabolic steroids
- decreased protein synthesis
- decreased muscle mass
- usually glucocorticoids: cortisol, prednisone
Adrenal gland components
- adrenal cortex (80%) –> steroid hormones
- adrenal medulla (20%) –> catecholamine synthesis, SNS regulation
Catecholamine synthesis
- released into blood
- fight or flight
- norepinephrine (cat)
- epinephrine (dog, human)
- increase metabolic rate
- increase blood pressure, cardiac contractility, myocardial excitablity
Pheochromocytoma
Tumor of adrenal medulla with excess production of catecholamines
Cortex components
- glomerulosa (15%)
- fasiculata (75%)
- reticularis (10%)
Glomerulosa
- specific enzyme: aldosterone synthase
- product: mineralocorticoids
Fasiculata
- specific enzyme: 17alpha-hydroxylase
- product: glucocorticoids, sex hormones
Reticularis
- specific enzyme: 17alpha- hydroxylase
- products: glucocorticoids, sex hormones
Steroids are degraded in the ______
Liver
- free hormone
- conjugated to glucuronide
- excreted thru urine, bile
- inhibited if diseased
Steroids are bound to proteins 94%, but only the ________ is active
Free hormone
Cortisol metabolism
- corticosteroid-binding globulin (CBG)
- albumin
- T1/2 < 2 hrs
Aldosterone metabolism
- albumin
- slightly bound
- T1/2 is 20 minutes
Steroidal mechanism of action
Free hormone diffuses into cell (lipophilic) –> binds cytoplasmic receptor –> translocates to nucleus, binds DNA –> directs transcription (proteins)
What are the cellular functions of cortisol?
- catabolic: gluconeogenesis, anti-insulin, protein
- anti-inflammatory
- anti-stress
- receptors in most cells*
Catabolic effects of cortisol on carbohydrates
- stimulates hepatic gluconeogenesis
- inhibits effects of insulin
- fight or flight
- protects from hypoglycemia
Catabolic effects of cortisol on lipids
- mobilizes fatty acids
- redistribution
Catabolic effects of cortisol on proteins
- inhibits cellular uptake of amino acids
- stimulates gluconeogenesis
- muscle breakdown
- skin, CT, bone
Anti-inflammatory/immunosuppressive function of cortisol
- stabilization of lysosomes
- decreases: capillary permeability, margination of WBCs
- suppression of T lymphocytes
- decreases fever (IL-1)
- blocks allergies
- give glucocorticoids during anaphylactic shock*
3 functions of cortisol
- resistance to stress
- stimulation of erythropoiesis
- maintenance of vascular tone
Functions of cortisol: summary
- gluconeogenesis
- protein catabolism
- stress resistance
- anti inflammatory
- immunosuppressive
The hypothalamic-pituitary-adrenal axis
Hypothalamus - corticotropin releasing hormone - physical, emotional, chemical stress Anterior pituitary - adrenocorticotropic hormone Adrenal gland - cortisol
Adrenocorticotropic hormone
Episodic secretion (concentration varies) - precursor: pro-opiomelanocortin (POMC)
ACTH mechanism of action
Increase free cholesterol –> conversion of cholesterol to pregnenolone –> major action of ACTH –> rate-limiting step in cortisol synthesis
- trophic effect
Increase stress in a normal dog results in:
Hypothalamus increases CRH –> pituitary increases ACTH –> adrenal increases cortisol
Feedback inhibition
- increased ACTH = decreased CRH
- increased cortisol = decrease CRH
- increased cortisol = decreased ACTH
Would you measure cortisol to determine if a dog has hypoadrenocorticism?
No, ACTH is secreted episodically so a normal dog could have a low cortisol
What happens if you give dexamethasone to a healthy dog?
Dex will suppress cortisol production, so the cortisol levels will be less than the level collected before the injection
Pituitary tumor
Will cause:
- increased ACTH
- bilaterally increase adrenals
- increase cortisol
________ is the most important endogenous mineralocorticoid
Aldosterone
- 90% of body’s mineralocorticoid effects
- some glucocorticoids have a small amount of mineralocorticoid effect
Aldosterone release is stimulated by
- decreased blood volume, decreased sodium
- increased potassium
Primary functions of aldosterone
- increased Na, Cl and water resorption
- increased K and H excretion
Aldosterone site of action
Principal cells of distal tubules and collecting ducts
- increase activity of basolateral Na/K ATPase
- increase transcription of luminal Na channels
Renin-angiotensin-aldosterone system (RAAS)
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
Aldosterone regulation
Hypovolemia –> increase renin –> stimulates conversion of angiotensinogen to angiotensin –> AG2 by angtiotensin converting enzyme –> AT2 stimulates production of aldosterone
