Adrenal gland, continued (L6) Flashcards
What is the primary action of mineralocorticoids?
Promote sodium retention by the kidney
Secondary result of sodium retention
Water retention
Primary endogenous MC
Aldosterone
11-deoxycorticosterone
Precursor of aldosterone that also has MC action
Aldosterone synthase - location
Primarily located in the zona glomerulosa of the adrenal cortices
Sites of action of aldosterone
Kidney
Colon
Salivary glands
Sweat ducts
Aldosterone effects on the kidney
Primary target. Retains sodium and water, excretes more potassium
Four steps in the renin-aldosterone-angiotensin pathway
- Decreased blood volume stimulates renin production from the juxtaglomerular apparatus
- Renin cleaves angiotensinogen to angiotensin I
- Angiotensin I is converted to angiotensin II by ACE
- AT-II is a vasoconstrictor and stimulates release of aldosterone
Aldosterone vs AVP
Aldosterone is a primary regulator of the blood volume, whereas AVP is more focused on free water volume
Primary high-affinity receptor for aldosterone
MR (nuclear receptor superfamily)
To what does the MR bind with high affinity?
Both MCs and GCs
Relative concentrations of GCs to MCs
GCs are 100-1000x higher than MCs, but over 95% are bound and aldosterone has no specific binding protein
Inactivation of glucocorticoids
Conversion of cortisol to cortisone by 11beta-HSD type 2 in the kidneys
Carbenoxolone
Inhibits 11beta-HSD type 2
Excessive licorice consumption
Licorice is also a natural inhibitor of 11-beta HSD type 2 and will lead to increased sodium and water retention if eaten too much
Adrenal androgen
DHEA(S): dehydroepiandosterone (sulfate)
What does DHEA get converted into?
Testosterone and estrogen
How many of total androgens come from the adrenal cortex in the prostate?
50%
When does androgen peak?
Between 20-30 years old
“Weak” androgens
DHEA: low affinity for androgen receptor
Pregnenolone
First compound in the synthesis of androgens; converted from cholesterol in the mitochondria
Cholesterol ester hydrolyase
Converts cholesterol ester to free cholesterol; enzyme is stimulated by ACTH
Rate-limiting step in steroid hormone biosynthesis
StAR protein moving cholesterol from the outer to the inner mitochondrial membrane; regulated by ACTH
Desmolase/P450scc
Converts cholesterol to pregnenolone
21-alpha-hydroxylase deficiency - hormone levels
Causes excess DHEA, no glucocorticoids, no mineralocorticoids
21-alpha-hydroxylase deficiency - clinical manifestations
Masculinization, ambiguous genitalia at birth, sodium loss
11-beta hydroxylase deficiency - hormone levels/gene involvement
CYP11B1 deficiency. Excess DHEA, no cortisol
11-beta hydroxylase deficiency - clinical manifestations
Salt and water retention due to excess MR activity
Low aldosterone due to low renin, high ANP
17-alpha hydroxylase deficiency - hormone levels
No adrenal androgens, decreased glucocorticoids, excess MCs
17-alpha hydroxylase deficiency - clinical manifestations
Feminization, sodium and water retention due to excess MR activity
What will all the adrenal enzyme deficiencies result in?
High ACTH levels due to lack of feedback
CYP11B2 stimulation
Stimulated by angiotensin II, not ACTH
Innervation of the adrenal medulla
Splanchnic nerve
Cellular architecture of the adrenal medulla
Cords of polyhedral epithelial cells
What is epinephrine released in response to?
Acute stress (pain, cold, perceived danger)
Speed of movement of epinephrine
Rapid release, rapid return
Locations of catecholamine synthesis
Dopamine can be converted to norepinephrine in the peripheral nerves, but epinephrine is ONLY made in the adrenal medulla
What stimulates conversion of NE to epi?
Cortisol
Through what types of receptors does epi act?
Both alpha and beta adrenergic receptors
Arousal effects of epi
Pupil dilation, sweating, GI and bronchial relaxation
Metabolic effects of epi
Increased glucose mobilization, increased BMR
Cardiovascular effects of epi
Vasoconstriction, tachycardia
Three main targets of epi
Muscle, liver, and fat
Half life of catecholamines
Very short: 10-90 seconds
Degradation of catecholamines
COMT or MAO
Metabolic byproduct of catecholamine breakdown
Vanillymandelic acid (VMA)
What is the clinical significance of VMA?
Has a longer half-life; can be used to detect tumors secreting NE or epi
Pheochromocytomas
Tumors in the chromaffin cells
Symptoms of pheochromocytomas
Hypertension without response to meds, headaches, tachycardia
Diagnosis of pheochromocytomas
Measurements of urinary metanephrines
Treatment of pheochromocytomas
Surgery. (Presurgery: alpha/beta blockers)
What is the nickname of pheochromocytomas?
The “10% tumor”
