Physiology Of The Adrenal Medullar And Cortex Flashcards
Superficial -> deep, what are the layers of the adrenal glands and what are they secrete
1) Zona glomerulosa
- Mineralcorticoids (aldosterone)
2) Zona fasciculata
- Glucocorticoids (cortisol)
3) Zona reticularis
- androgens (DHEA/androstenedione)
4) adrenal medulla
- catecholamines (epinephrine and Norepinephrine)
(Note the glucocorticoids and androgens have overlap with being produced in zones 2-3. However the majority is produced in their respective zones)
Brief overview of how the nervous system works
Somatic
- uses Ach as the neurotransmitter and N1 receptors on target skeletal muscles to induce action
- DOESNT use peripheral ganglia or nerves and only synapses into sympathetic chain
Parasympathetic autonomic
- uses Ach as the neurotransmitter and M receptors on smooth muscle/cardiac muscles and glands
- presynaptic ganglion is on the target organ/tissue.
Sympathetic autonomic
- uses Ach and N2 receptors for presynaptic and NE and a/b adrenergic receptors found on
On smooth muscles/cardiac muscles and glands
- synapse onto sympathetic chain and go to the respective tissues
- *the adrenal gland is the exception which uses epinephrine as its postsynaptic neurotransmitter and presynaptic neurons bind directly on the adrenal medulla.
- presynaptic neurons use Ach on adrenal medulla N2 receptors.**
How does epinephrine and norepinephrine differ with effects on the cardiovascular system
1) both increase arterial pressure but in different ways
2) epinephrine = increase in heart rate and cardiac output. Decreases Total peripheral resistance
3) norepinephrine = decreases heart rate and cardiac output. Increases Total peripheral resistance
Epinephrine prefers B adrenergic receptors (hence the heart rate increase and cardiac output)
Norepinephrine prefers a-adrenergic receptors (hence the increase in TPR)
Pheochromocytoma vs neuroblastoma
Pheochromocytoma
- rare neoplasm formed in chromaffin cells in adrenal medulla
- most common adrenal medulla tumor in adults
Neuroblastoma
- neoplasm of neural crest cells that can be found anywhere along the sympathetic chain
- most common adrenal medulla tumor in children
What are common triggers for the hypothalamus to release CRH
Stress, inflammation, trauma, fever, psychological stress
Results in cortisol increased which results in
- increased gluconeogenesis and prevents glucose from being reuptake
- increase lipolysis
- protein catabolism
- vasoconstriction via a1 receptor upregulation
Upregulation of a1 receptors has a synergistic effects with epinephrine
CRH is released via paraventricular nucleus (along with oxytocin)
Anti-inflammatory effects of cortisol
Stabilizes lysosomes
Inhibits phospholipase A2
Decreases prostaglandins, leukotreines, arachidonic acid.
Inhibits IL-2 production
Inhibits histamine
CRH receptor and cellular action
Receptor is found on surface of corticotrophs on anterior pituitary gland
The receptor is a Gs protein coupled receptor which upregulates AC and cAMP actions
- also upregulates PKA and end goal is to increase intracellular calcium which promotes ACTH release from vesicles
ACTH receptor and cellular effects
Melanocortin-2 receptor is the same receptor for ACTH and is found on the surface of adrenal cortex cells in the zona fasiculata
These receptors are Gs protein-coupled and upregulate AC/cAMP
- end goal is to increase activity of P-450 cytochrome proteins and synthesis of several enzymes (specifically cholesterol desmolase)
How to diagnosis hypercortisolism
Measure 24 hr urine cortisol and salivary cortisol levels
If its high, measure ACTH
- if low = ACTH independent cushing syndrome
- if high = ACTH dependent cushing syndrome
If ACTH dependent cushing, give high dose dexamethasone (analog of cortisol) test
- if ACTH goes DOWN = cushing disease
- if ACTH goes UP = ectopic ACTH secretion (almost always small cell lung cancer)
- *this makes sense because giving cortisol turns off the axis, but NOT the ectopic tissue**
Causes of ACTH independent = exogenous corticosteroid use or adrenal primary tumor
Cushing disease means what?
Pituitary corticotroph Adenoma or carcinoma that secretes excess ACTH
- ACTH will be suppressed with high dose dexamethasone test**
What is conn syndrome
Hyperaldosteronism via primary adrenal gland tumors or secondary pituitary tumors
difference between primary and secondary is that primary = low renin and secondary = high renin
Characteristized by:
- hypernatremia
- hypokalemia
- metabolic alkalosis (due to excessive H+ dumping)
Treatment = spironolactone
What is the rate limiting step of aldosterone
Cholesterol -> pregnenolone
- uses cholesterol desmolase enzyme
- induced by ACTH
What is the final step of aldosterone synthesis
Corticosterone -> aldosterone
- uses aldosterone synthase enzyme
- induced by angiotensin-2 and hyperkalemia
What are the rate limiting steps for permanently putting cholesterol into he cortisol synthesis pathway?
1) Pregnenolone -> 17-hydroxypregnenolone
2) progesterone -> 17-hydroxyprogesterone
BOTH steps require 17a-hydroxylase enzymes
What are the common enzymes in both aldosterone and cortisol synthesis
3B-hydroxysteroid dehydrogenase
- this is the only enzyme that is found also in sex steroid production (all 3 hormones of the adrenal gland)
21B hydroxylase
11B hydroxylase
Why do glucocorticoids, despite being in higher levels than Mineralcorticoids and also being able to bind to MR receptors, NOT produce Mineralcorticoid effects?
Because under normal conditions, enough cortisol in the body is irreversibly converted into cortisone via 11B hydroxysteroid dehydrogenase enzymes
Cortisone has the same efficacy on glucocorticoid receptors as cortisol, but much less on Mineralcorticoid receptors
- *loss of 11B-HSD enzyme results in appaeratn Mineralcorticoid excess despite low levels of aldosterone in the body**
- due to excess cortisol and no cortisone.
What is a natural inhibitor of aaB-hydroxysteroid dehydrogenase enzymes?
Glycyrrhetinic acid which is found in black licorice
Therefore, if someone feasts on black licorice in high levels, will cause apparent hyper aldosteronism
- hypernatremia
- hypokalemia
- high blood pressure
- metabolic acidosis
What does virilization mean?
Masculinization of phenotype, especially external genitalia
What happens in 17a-hydroxylase Deficency
In ability to convert cholesterol in cortisol or sex androgens
- leads to major excess of aldosterone
Symptoms:
- Addison’s disease symptoms
- hypernatremia and high BP and hypokalemia
- feminization of external genitalia
