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68 Cards in this Set
- Front
- Back
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what is the primary stumuli for aldosterone
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high blood K or high angiotensin 2
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what is the negative feedback exerted by cortisol
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inhibits ACTH, CRH, and the immune system
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what is aldosterone's role in the distal tubule
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aldosterone regulatess the transcription of Na/K ATPase and Na/Cl symport
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how is Na pumped in the distal tubule
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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
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where will aldosterone work
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anywhere we have to regulate fluid and electrolytes (kidney, sweat glands, GI, salivary gland)
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what is the main role of a nuclear Rc
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transcription and translation
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what happens if we have a high amount of K
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aldosterone is secreted and we secrete K and take up Na
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what are the aldosterone induced proteins
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Na channel
Na/K ATPase |
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what is aldosterones minor activity
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stimulates Na/Cl symport, Na/K ATPase, Na channel
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what AIP are found in the collecting tubule (late distal tubule)
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Na channel
Na/K ATPase |
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what do we make more of glucocorticoids or mineralcorticoids
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glucocorticoids
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what converts cortisol to cortisone
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11BHSD2
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what insures we have some speceficity at our mineral corticoid Rc for aldosterone
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11BHSD2 this is found anywhere aldosterone is the main action (kidney, salivary/sweat gland, GI)
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when the Gluc Rc is empty where is it found
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in the cytoplasm bound to proteins
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what happens to the Gluc Rc when a glucocorticoid binds
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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
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what are glucocorticoids mainly used as
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antiinflammatory (inhibit inflammatory genes)
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when gluc rc binds to DNA and activation occurs what happens
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mRNA is made which will then get transcribed into protein
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how can 11BHSD2 be overcome
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by saturating the system with a high amount of cortisol
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how can Gluc/Gluc Rc carry out repression
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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 |
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what is an aldosterone induced protein regardless of its location
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Na/K ATPase
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what are glucocorticoids mainly used for
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antiinflammatory
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what is the set of steps in the HPA axis
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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 |
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what upregulates/stimulates CRH release
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5-HT (seritonin), NE (depending on adreno Rc location), ACh
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what downregulates/inhibits CRH release
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GABA, high cortisol levels
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what does cortisol do to the immune system
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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) |
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why are glucocorticoids given to treat fetal lungs
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since their lungs haven't fully developed they are given dexamethasone/glucocorticoid which stimulates surfactant production
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what diseases happen when you have excess cortisol and what can be causes of cortisol excess
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cushing syndrome
high cortisol may be due to adrenal tumor, or taking high doses of glucocorticoids for a long time |
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what diseases happen when you have excess aldosterone
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excess aldosterone causes us to absorb Na and fluids causing an increase in plasma volume and therefore we have HIGH BLOOD PRESSURE
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what can cause a deficiency in aldosterone or cortisol
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adrenal insufficiency
addison's disease |
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how does aldosterone effect cardiac remodeling
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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 |
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how does aldosterone excess increase BP
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increases plasma volume via reabsorbing Na and fluids
enhances angiotensin activity on blood vessels causing more contraction which contributes to a increase in BP |
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does aldosterone have an effect on glucocorticoids
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no
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what all does excess aldosterone effect
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high bp
fibrosis of heart effects vasoactive mediators (angiotensin 2) |
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what is cushings syndrome caused by
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excess cortisol
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what is addison's disease/adrenal insufficiency
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lose ability to make either mineral or glucocorticoids
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what is the cause of a primary defect in adrenal insufficiency
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adrenal defect, addison's disease, surgical removal of adrenal gland
viral infections may also kill off cells in adrenal gland which make gluc/mineralcorticoids |
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what is the cause of a 2nd and 3rd defect in adrenal insufficiency
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2nd - defect in pituitary therefore not making ACTH
3rd - defect in hypothalamus therefore not making CRH |
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why can cortisol create problems such as high blood pressure
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because its equal in its Na retention and inflammatory properties
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what are the short acting corticosteroids
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cortisol
cortisone fludrocortisone |
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what are the intermediate acting corticosteroids
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prednisone
prednisolone 6 alpha methylprednisolone |
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what are the long acting corticosteroids
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dexamethasone
betamethasone |
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what are the symptoms seen in acute adrenal insuficiency
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n/v, ab pain, dehydration (b/c no reabsorbing Na therefore no water)
hyperkalemia hyponatremia acidosis |
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how do you treat acute adrenal insufficiency
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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 |
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how do you treat chronic adrenal insufficiency
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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 |
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what can be given as a substitute for aldosterone
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fludrocotisone
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what are the systemic uses for glucocorticoids
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adrenal insufficiency
endocrine disorder removal of gland adrenal tumor no zona fasciculata |
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what are the non-endocrine uses of glucocorticoids as drugs
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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 |
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what is the growth factor of the adrenal zona fasciculata
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ACTHq
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what is a side effect associated w/ high doses of Glucocorticoids (systemic use)
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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..
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what is the effect of glucocorticoids on gluconeogenesis
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glucocorticoids upregulate gluconeogenesis and make us a little insulin resistant so we may look like we have diabetes
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what are the properties of fludrocortisone
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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 |
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why is fludrocotisone not used for its anti inflammatory effects
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because glucocorticoids do things in the liver muscle etc w/ other hormones
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what are the properties of bethamethasone and dexamethasone
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long acting corticosteroid
potent antiinflammatory no Na retention good if we want to fight infection w/o raising BP |
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what kind of glucocorticoid is used in pregnancy and can cross the placenta
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florinated glucocorticoids
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what type of topical glucocorticoids can cross the skin rapidly
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fluorinated
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why are topical glucocorticoids safe
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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
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what are some examples of topical glucocorticoids
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bethamethasone
hydrocortisone triamcinolone (kenalog) |
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what glucocorticoids can be used for irisitis, uveitis
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prednisolone
dexamethasone fluoromethalone medrysone |
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what drugs are inhaled (lung nasal) steroids (glucocorticoids)
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fluticasone, budesonide, beclomethasone, mometasone
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how do glucocorticoids reduce allergic reactions
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try to offset all the leukocytes coming in and releasing those things that cause inflammation
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what does a spacer device do
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slows down particle speed so they don't just crash into the back of the throat
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what can cholesterol form
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androgens
aldosterone cortisol |
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what inhibits the 1st step in cholesterol conversion
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aminoglutethimide (AGT) inhibits P450
ketoconazole inhibits P450 too |
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what is ketoconazole usually used for
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usually used as an antifungal
used at a lesser concentration when used to treat corticoid excess (adrenolytic therapy) |
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what does a high dose of ketoconazole do
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suppresses adrenal function
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what inhibits the production of cortisol
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metryapone
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what kind of patients would be given a high dose of glucocorticoids
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patients fighting lymphomas
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what are the drug interactions with adrenal croticoids
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insulin
isoniazed oral hypoglycemics |
