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68 Cards in this Set

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what is the primary stumuli for aldosterone
high blood K or high angiotensin 2
what is the negative feedback exerted by cortisol
inhibits ACTH, CRH, and the immune system
what is aldosterone's role in the distal tubule
aldosterone regulatess the transcription of Na/K ATPase and Na/Cl symport
how is Na pumped in the distal tubule
the Na/K ATPase pumps Na into to blood from the interstitial creating a gradient allowing Na to get pumped in via the Na/Cl symport from the urine
where will aldosterone work
anywhere we have to regulate fluid and electrolytes (kidney, sweat glands, GI, salivary gland)
what is the main role of a nuclear Rc
transcription and translation
what happens if we have a high amount of K
aldosterone is secreted and we secrete K and take up Na
what are the aldosterone induced proteins
Na channel
Na/K ATPase
what is aldosterones minor activity
stimulates Na/Cl symport, Na/K ATPase, Na channel
what AIP are found in the collecting tubule (late distal tubule)
Na channel
Na/K ATPase
what do we make more of glucocorticoids or mineralcorticoids
glucocorticoids
what converts cortisol to cortisone
11BHSD2
what insures we have some speceficity at our mineral corticoid Rc for aldosterone
11BHSD2 this is found anywhere aldosterone is the main action (kidney, salivary/sweat gland, GI)
when the Gluc Rc is empty where is it found
in the cytoplasm bound to proteins
what happens to the Gluc Rc when a glucocorticoid binds
glucocorticoid is lipid soluble and once it binds to the gluc Rc, the gluc Rc disassociates from the proteins and travels to the nucleus where it dimerizes and acts a transcription factor
what are glucocorticoids mainly used as
antiinflammatory (inhibit inflammatory genes)
when gluc rc binds to DNA and activation occurs what happens
mRNA is made which will then get transcribed into protein
how can 11BHSD2 be overcome
by saturating the system with a high amount of cortisol
how can Gluc/Gluc Rc carry out repression
once the Gluc Rc binds to the GRE it can recruit repressors

Gluc/Gluc Rc can bind to a promotor region other than GRE that it has an affinity for and prevent other transcription factors from binding there

Gluc/Gluc Rc can also bind to a transcription factor it has an affinity for and prevent it from binding to its promotor region

IN ALL CASES GENE IS NOT ACTIVATED
what is an aldosterone induced protein regardless of its location
Na/K ATPase
what are glucocorticoids mainly used for
antiinflammatory
what is the set of steps in the HPA axis
CRH is released from the hypothalamus

CRH acts on the corticotropes in the Anterior pituitary

Corticotropes secrete POMC which gets cleaved into ACTH

ACTH acts on the fasiculata cells in the adrenal cortex

the fasiculata cells secrete cortisol
what upregulates/stimulates CRH release
5-HT (seritonin), NE (depending on adreno Rc location), ACh
what downregulates/inhibits CRH release
GABA, high cortisol levels
what does cortisol do to the immune system
when we have an infection/inflammation monocytes, macrophages, lymphocytes, neutrophils secrete cytokines (IL 1, 2, 6) and TNF ALPHA

IL 1,2,6 and TNF ALPHA will stimulate CRH and ACTH production resulting in cortisol production

when cortisol gets high it will inhibit the immune system from producing those cytokines (inflammatory genes)
why are glucocorticoids given to treat fetal lungs
since their lungs haven't fully developed they are given dexamethasone/glucocorticoid which stimulates surfactant production
what diseases happen when you have excess cortisol and what can be causes of cortisol excess
cushing syndrome

high cortisol may be due to adrenal tumor, or taking high doses of glucocorticoids for a long time
what diseases happen when you have excess aldosterone
excess aldosterone causes us to absorb Na and fluids causing an increase in plasma volume and therefore we have HIGH BLOOD PRESSURE
what can cause a deficiency in aldosterone or cortisol
adrenal insufficiency
addison's disease
how does aldosterone effect cardiac remodeling
certain diuretics are antagonist at mineral corticoid Rc and have beneficial changes where they limit the amount of fibrosis in the heart

SINCE ALDOSTERONE IS AN ANTIDIURETIC IT INCREASES CARDIAC REMODELING CAUSING FIBROSIS
how does aldosterone excess increase BP
increases plasma volume via reabsorbing Na and fluids

enhances angiotensin activity on blood vessels causing more contraction which contributes to a increase in BP
does aldosterone have an effect on glucocorticoids
no
what all does excess aldosterone effect
high bp
fibrosis of heart
effects vasoactive mediators (angiotensin 2)
what is cushings syndrome caused by
excess cortisol
what is addison's disease/adrenal insufficiency
lose ability to make either mineral or glucocorticoids
what is the cause of a primary defect in adrenal insufficiency
adrenal defect, addison's disease, surgical removal of adrenal gland

viral infections may also kill off cells in adrenal gland which make gluc/mineralcorticoids
what is the cause of a 2nd and 3rd defect in adrenal insufficiency
2nd - defect in pituitary therefore not making ACTH

3rd - defect in hypothalamus therefore not making CRH
why can cortisol create problems such as high blood pressure
because its equal in its Na retention and inflammatory properties
what are the short acting corticosteroids
cortisol
cortisone
fludrocortisone
what are the intermediate acting corticosteroids
prednisone
prednisolone
6 alpha methylprednisolone
what are the long acting corticosteroids
dexamethasone
betamethasone
what are the symptoms seen in acute adrenal insuficiency
n/v, ab pain, dehydration (b/c no reabsorbing Na therefore no water)
hyperkalemia
hyponatremia acidosis
how do you treat acute adrenal insufficiency
giving electrolytes and 5% hydrocortisone

hydrocortisone is given in a high enough dose to act on the mineral corticoid Rc

in the collecting tubule cortisol will act like aldosterone and cause the expression of the Na channel and Na/K ATPase causing more K to be secreted and more Na to be reabsorbed
how do you treat chronic adrenal insufficiency
give oral glucocorticoids (hydrocortisone/cortisone) and you give just enough so you can add a little Na and use the glucocorticoids to sub for aldosterone

fludrocortisone can be used because it has 120x more Na stimulation than cortison and can be subbed for aldosterone
what can be given as a substitute for aldosterone
fludrocotisone
what are the systemic uses for glucocorticoids
adrenal insufficiency
endocrine disorder
removal of gland
adrenal tumor
no zona fasciculata
what are the non-endocrine uses of glucocorticoids as drugs
certain leukemia/lymphomas (immature T cells are very sensitive to glucocorticoids and will undergo apoptosis)

suppress inflammation or immune response (can be used to treat allergy)

can be used in new borns to upregulat surfactants

can be give to someone undergoing thyroid storm
what is the growth factor of the adrenal zona fasciculata
ACTHq
what is a side effect associated w/ high doses of Glucocorticoids (systemic use)
if given a high amount of GC chronically the HT and AP are turned off therefore we're not making CRH or ACTH and no ATCH which is the growth factor for the adrenal zona fasiculata means the function and activity of this zone starts to diminish and gland shrivels. THIS IS WHY THE DOSE IS TAPERED IN ORDER TO BRING BACK ADRENAL FXN..
what is the effect of glucocorticoids on gluconeogenesis
glucocorticoids upregulate gluconeogenesis and make us a little insulin resistant so we may look like we have diabetes
what are the properties of fludrocortisone
short acting corticosteroids
it has antiinflammatory activity but we only use it when we need to resuply aldosterone

more selective for mineral corticoid receptor and is used when we need Na retention or when we have adrenal insufficiency and aren't making aldosterone
why is fludrocotisone not used for its anti inflammatory effects
because glucocorticoids do things in the liver muscle etc w/ other hormones
what are the properties of bethamethasone and dexamethasone
long acting corticosteroid
potent antiinflammatory
no Na retention
good if we want to fight infection w/o raising BP
what kind of glucocorticoid is used in pregnancy and can cross the placenta
florinated glucocorticoids
what type of topical glucocorticoids can cross the skin rapidly
fluorinated
why are topical glucocorticoids safe
because they have little systemic penetration because they get metabolized at the site (skin, nose, etc) so they don't accumulate at high levels in the blood stream
what are some examples of topical glucocorticoids
bethamethasone
hydrocortisone
triamcinolone (kenalog)
what glucocorticoids can be used for irisitis, uveitis
prednisolone
dexamethasone
fluoromethalone
medrysone
what drugs are inhaled (lung nasal) steroids (glucocorticoids)
fluticasone, budesonide, beclomethasone, mometasone
how do glucocorticoids reduce allergic reactions
try to offset all the leukocytes coming in and releasing those things that cause inflammation
what does a spacer device do
slows down particle speed so they don't just crash into the back of the throat
what can cholesterol form
androgens
aldosterone
cortisol
what inhibits the 1st step in cholesterol conversion
aminoglutethimide (AGT) inhibits P450
ketoconazole inhibits P450 too
what is ketoconazole usually used for
usually used as an antifungal

used at a lesser concentration when used to treat corticoid excess (adrenolytic therapy)
what does a high dose of ketoconazole do
suppresses adrenal function
what inhibits the production of cortisol
metryapone
what kind of patients would be given a high dose of glucocorticoids
patients fighting lymphomas
what are the drug interactions with adrenal croticoids
insulin
isoniazed
oral hypoglycemics