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
