Flashcards in Mineralocorticoids and Aldosterone Deck (37):
What are the three layers of the adrenal cortex?
What does the zona glomerulosa do?
Produces mineralocorticoids (aldosterone)
What does the zona fasciculata do?
Produces glucocorticoids (cortisol) and androgens
What does the zona reticularis do?
Specialized to secrete Dihydroepiandrosterone
What does the adrenal medulla do?
Small amount of norepinephrine
Largest region of the cortex?
Key enzyme in the zona glomerulosa needed for mineralocorticoids?
Key enzyme in the zona fasciculata needed for cortisol?
What is the common step to formation of all the steroids?
StAR needed for cholesterol to produce Pregnenolone
Most common abnormalities to form adrenal gland dysfunction?
What is the first step in steroid synthesis?
Get cholesterol into the mitochondria
What transports cholesterol into the mitochondria?
What generates Pregnenolone from cholesterol?
Cholesterol side-chain cleavage enzyme
G: Salt (mineralocorticoids)
F: Sugar (glucocorticoids)
R: Sex (androgens)
What does ACTH stimulate production of?
Both cortisol and adrenal androgens
What is the feedback for ACTH inhibition?
No androgen feedback to inhibit ACTH
What receptor does ACTH stimulate?
MC2R (melanocortin-2 receptor)
What is the primary mediator of aldosterone release?
A-II; less so by ACTH and K+ levels
Three actions of aldosterone on the kidneys:
1.) Sodium and therefore passive water reabsorption
2.) Potassium absorption by the principal cells of the cortical CT
3.) Active secretion of protons via proton ATPases in lumenal membrane of IC of CT
Three major pathways regulating the secretion of renin by granular cells at the JGA:
1.) Renal baroreceptors: decreased perfusion = increased renin
2.) Macula densa: decreased Na/Cl ions in DCT = increased renin
3.) Sympathetic nervous system: increased activity increased renin release via beta receptors
How does A-II cause aldosterone release?
A-II binding to AT1 receptor causing IP3 binding to IP3R and release of intracellular Ca2+
What is the indirect method by which aldosterone inhibits ACTH release?
Systems effects of regulating blood volume and blood pressure leads to inhibition of ACTH release
What do principle cells express?
What does 11beta-HSD2 cause?
Breaks down glucocorticoids so that they do not have as high of an affinity to the same receptors as mineralocorticoid receptors
What does glycyrrhetinic acid do?
What is a common glycyrrhetinic acid?
Half-life of aldosterone:
What is Conn's syndrome?
What causes Conn's syndrome?
Autonomous benign tumors of the adrenal gland hyper-secrete aldosterone
What does Conn's syndrome cause?
Hypertension bc H20 and Na+ retention and hypokalemia bc excess K+ secretion and suppressed renin release
What is secondary hyperaldosteronism?
What can cause secondary hyperaldosteronism?
Decrease in effective arterial blood volume associated with ascites or heart failure leading to continuous stimulation of RAS system
What can cause primary hypoaldosteronism?
Plasma renin levels elevated due to primary adrenal insufficiency
What can cause secondary hypoaldosteronism?
Inadequate stimulation of aldosterone secretion despite normal adrenal function
How can mineralocorticoids cause kidney damage?
Production of ROS either by stimulation of NADPH oxidase or via mitochondria
What do ROS activated by mineralocorticoids cause in the kidney?
Podocyte damage, inflammation and fibrosis