Komiskey: Corticosteroids and Mineralocorticoids; Kidney Flashcards
How does stress affect release of cortisol?
Stress activates corticotrophin-releasing hormone (CRH)–> Adrenocorticotrophic hormone (ACTH) –> Cortisol+DHEA
Cortisol is negative feedback for CRH
Cortisol action?
Decrease inflammation; suppresses immune function
What time of day is cortisol highest in the plasma?
2 peaks between 6 am and 10am. (breakfast time)
What is the most abundant (yet ignored) steroid hormone?
What does it do?
DHEA (Dehydroepiandrosterone)
Cells use it to make testosterone and estradiol; levels decline due to age, stress, disease.
Reduces abdominal fat; anabolic: builds tissues; reduces pain by restoring natural endorphins; anti-cancer effects in animals
What are the more serious side effects of DHEA when taken as a supplement?
could abnormally increase testosterone: acne, testicular atrophy, increased risk of prostate cancer (women: acne, facial hair)
DHEA can also be converted into estrogen: gynecomasty; increased risk of breast cancer
DHEA is misleadingly marketed as an anabolic steroid; but the anabolic properties are due to DHEA being an androgen precursor which makes testosterone, which is what has anabolic properties; not straight DHEA. testosterone. but it’s not advertised that way.
What are the key effects of mineralocorticoids?
increase in Na+ retention: where salt goes, water follows
- -> volume expansion
therefore: potassium and hydrogen ion loss
Common mineralocorticoid agent and it’s uses?
Fludrocortisone
potent salt retaining activity
Addison’s disease (adrenocortical insufficiency)
What happens in adrenocortical overactivity?
- Cushing’s syndrome or adrenal hyperfunction
- Cushing’s DISEASE or pituitary basophilism: buffalo obesity, easy bruises (ecchymoses), impotence or amenorrhea, OSTEOPOROSIS
What is the primary stimulus for aldosterone synthesis?
Activation of RAAS in response to hypovolemia
increase in plasma K+ will increase aldosterone
How can an aldosterone antagonist agent aid in the treatment of chronic heart failure?
prevent remodeling/prevent heart from becoming fibrotic
Aldosteronism (hyperaldosteronism)
Conn’s syndrome: small adenomas of zona glomerulosa; hypertension, hypernatremia, hypokalemia, alkalosis
Conn’s Tumor: Primary hyperaldosteronism - a benign unilateral tumor of the adrenal cortex
2 forms of pseudoaldosteronism?
Liddle syndrome: mutation of the epithelial Na channel causing uncontrolled increased activity: sodium leads to decrease in renin and ultimately a decrease in aldosterone (opposite to Conn’s syndrome where aldosterone is elevated)
Acquired: licorice eaters (glycyrrhizin and glycyrrhetic acid) - licorice consumption contraindicated in patients taking ACE-I
Where is renin made and stored?
JG cells
What prevents mineralocorticoid receptors (MR) from binding glucocorticoids since there presence in plasma is much higher than mineralocorticoids?
11B OH II
- it is present in aldosterone target cells and metabolizes glucocorticoids to a form that doesn’t bind MRs
Genetic defects of this enzyme (or licorice): pseudo-hyperaldosteronism state (severe HTN). Glucocorticoids saturate MR and greatly increase aldosterone effect
What are drugs for anti hypertension that block MRs?
Spironolactone (more SE) or Eplerenone
Used for secondary HTN caused by hyperaldosteronism
