L73: HPA Axis & Adrenal (part II) Flashcards
What is the biologically active precursor of Aldosterone
11-DOC
What enzyme deactivates cortisol into cortisone?
11B-HSD2
What enzyme deactivates cortisol into cortisone, in mineralocorticoid target cells?
11B-HSD2.
The big idea here is that cortisol isn’t supposed to act on mineralocorticoid target cells, but glucocorticoid target cells.
What enzyme reactivates cortisone to cortisol, in glucocorticoid target cells?
11B-HSD1
What drug inhibits 11B-HSD2, resulting in excess MR activation?
Carbenoxolone
What does licorice do?
Inhibits 11B-HSD2, thereby preventing the inactivation of cortisol to cortisone in MR target cells.
What does licorice (glycrrhetinic acid) do?
Inhibits 11B-HSD2, thereby preventing the inactivation of cortisol to cortisone in MR target cells.
What are the 3 layers of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
“GFR”
What layer of the adrenal cortex makes mineralocorticoids (eg. Aldosterone)?
Zona glomerulosa
What layer of the adrenal cortex makes glucocorticoids (eg. cortisol)?
Zona fasciculata
What innervates the adrenal medulla?
Splanchnic nerve
High ACTH and no cortisol. This drives the synthesis of
norepinephrine
Only in the adrenal medulla, cortisol stimulates the conversion of
norepinephrine to epinephrine.
High ACTH and no cortisol. This drives the synthesis of
norepinephrine (normally Epi is the dominant one)
21a hydroxylase deficiency
Congenital Adrenal Hyperplasia
Hypotension Hyperkalemia High plasma renin Masculinization High ACTH
CAH
Hypertension
Hypokalemia
Masculinization
High ACTH
2nd most common cause of CAH:
CYP11B1: 11-hydroxylase deficiency
Hypertension
Hypokalemia
Masculinization
High ACTH
2nd most common cause of CAH:
CYP11B1, 11-hydroxylase deficiency
What is the metabolic byproduct of catecholamine catabolism by COMT and MAO, that is excreted in urine?
VMA (vanillylmandelic acid)
High urinary VMA may indicate
EPI/NE producing tumors
Pheochromocytoma
tumor originating from chromatin cell
Pheochromocytoma
tumor originating from chromatin cell.
Why is pheochromocytoma called a “10% tumor”?
10% are malignant 10% are bilateral 10% in children 10% familial 10% recur 10% associated with MEN 10% present with a stroke 10% extra-adrenal
ONLY IN THE ADRENAL MEDULLA, cortisol stimulates the conversion of
norepinephrine to epinephrine.
What do patients with 21a-hydroxylase or 11beta-hydroxylase deficiencies have in common?
Excess ACTH (lack of negative feedback, since no cortisol)
Steroidogenic regulatory protein
transfers cholesterol from the outer mitochondria to the inner mitochondria
Which of the following is regulated by ACTH? A. StAR B. Cholesterol ester hydrolase C. ....add more D. All of the above
D.
What zone of the adrenal gland does 11-hydroxylase (CYP11B1) live?
Z. fasciculata
What zone of the adrenal gland does CYP11B2 11-hydroxylase live?
Z. glomerulosa
Where in the adrenal gland is 17alpha-hydroxylase (CYP17)
Z. fasciculata and reticularis
Is 11B-HSD1 and 2 in the p450 family? Where does it live?
No. Kidney (type 2)
What’s another name for aldosterone synthase?
CYP11B2
Where does CYP11B2 live?
Zona glomerulosa
Adrenal medulla is derived from
neural crest cells
Preganglionic neuron to adrenal neuron comes from
splanchnic nerve
Rate limiting step for dopamine synthesis?
Tyrosine hydroxylase
High ACTH but low cortisol. Will you lack:
A. Dopamine
B. NE
C. Epi
C. Epi
George has high BP that is unresponsive to BP lowering meds. What should you check for?
Look at VMA in urine. Think: Pheochromocytoma is unresponsive to B-blocker
