Endo 1 Flashcards
Cholesterol Synthesis to pregnenolone
Requires cholesterol desmolase being activated by ACTH
-Key rate limiting step
Cholesterol Synthesis to pregnenolone
Requires cholesterol desmolase being activated by ACTH
-Key rate limiting step
How do I get to Corticosterone from pregnenolone
3 B hydroxysteroid dehydraogenase
21 B hydroxylase
11 B hydroxylase
- if any of these are deficient, will shunt to Cortisol and sex steroids
How do I get from pregnenolone to cortisol
17 a hydroxylase,
21 B hydroxylase
11 B hydroxylase
If I am deficient in 17 a hydroxylase, what happens?
Shunt to aldosterone
If I am deficient in 17 a hydroxylase, what happens?
Shunt to aldosterone
If im deficient in 21 B hydroxylase what happens
Shunt to sex steroids only
11 B hydroxylase deficiency, what happens
Shunt to sex steroids only
If im deficient in 17 20 lyase, what happens
Shunt to cortisol and aldosterone
How do I get from corticosterone to aldosterone (last step in forming aldosterone)?
Aldosterone synthase is stimulated by angiotensin II (RAS)
From superficial to deep, what is the adrenal gland cortex
Aldosterone top - G glomerulosa
Cortisol middle - F fasiculata
DHEA bottom - R reticularis
ACTH stimulates ultimately what hormones to be released
All of them in the adrenal cortex
When aldosterone is created in the cortex, what does it do
Travel through the blood to the distal tubules of the kidney to cause transcription of sodium transport channels.
Inserts sodium channels in DCT.
Then it excretes K to retain Na and increase volume/blood pressure
What stimulates the RAAS system
Low renal perfusion from low blood volume.
Hyperkalemia.
How does aldosterone negative feedback work?
Increased blood volume
Increased BP
Increased sodium
Or low potassium
Then
Negative feedback on CRH
Decreased released of ACTH
Decreased release of aldosterone
Where are androgens produced
DHEA, DHEAS, and androstenedione (not corticosterone)
In the cortex in both genders. Produced mostly by the zonal reticularis. Some produced by zonal fasciculate
produced in the gonads. Produced by gonads in males and adrenal cortex in both M and F
DHEA and DHEAS function
Less potent.
Secondary sex characteristics in adolescence and childhood
What does a deficiency in 17 ketosteroid reductase cause
Absence of testosterone
Precursor to both estrogen and testosterone
Androstenedione
During puberty you get pulsatile release of what
CRH, which gives you an abundance of ACTH to get secondary sex characteristics
In general how is CRH released outside of certain periods in puberty
Pulsatile on a day to day basis.
Pulses before waking. - help to wake up
In response to stressors. - need stress to fight the bear.
What does glucocorticosteriod mean
Gluco means sugar, cortico means steroid.
Function is to mobilize sugar.
Cortisol is a glucocorticosteriod
What does mineralcorticosteriod mean
Mineral means things like potassium
Cortico means steriod.
Example is aldosterone
What does cortisol bind to and its effect on hormones
It binds to glucocorticosteroid receptor with high affinity
It binds to mineralcorticosteroid receptor with low affinity.
When concentration is high enough it will have same effect on kidney as aldosterone.
Cortisol actions on the body
Gluconeogensis; protein metabolism and dec protein synthesis. Also break down fat for same thing. Mobilize aa to liver for gluconeogenesis
- mobilizing energy
Anti insulin. Cause insulin insensitivity
Anti inflammatory by inhibit release of histamine and serotonin from mast cells. Incr synthesis of A2 inhibitor. Inhibit syn of IL2. Inhibit prod. Of T lymphocytes. Inhib precursor of prostaglandin.
IL 2 is a cytokine, serotonin causes vasodilation. Prostaglandin increases pain and fever. So want to inhibit these
Increase vascular response to catecholamines. Upregulates a1 receptors on arterioles whicj incr. sens to NE. ; excess of cortisol causes incr arterial pressure
Why does adrenal hypertrophy happen with high ACTH (chronically)
Overtime, ACTH up-regulates its own receptor. It does this to increase sensitivity of ACTH
For example its like having a tumor that continuously pumps out cortisol regardless of negative feedback
Why does dexamethasone suppression test work
When you give a low dose of dexamethasone to a patient before bed, their ACTH hypertrophy or tumor should act independently if the negative feedback
What should happen normally after a dexamethasone suppression test
They should wake up with low ACTH, low CRH because CRH is inhibited by negative feedback. Only if the negative feedback is working.
If not working, ACTH and CRH would keep pumping independent of the negative feedback loop
Depends if you give a high or low dose of dexa though and the underlying path if its a tumor of the adrenal cortex or ACTH secreting tumor
ARE catecholamines UNDER CONTROL by the HPA axis?
No,
Act independently of it
What are catecholamines released by
Cheomaffin cells which synthesize cat crom amino acid tyrosine
1:4 ratio of NE to Epi
