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18 Cards in this Set
- Front
- Back
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Glucocorticoids |
Regulate glucose metabolism Anti-inflammatory - Cortisol |
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Mineralocorticoids |
Regulate H2O salt balance & blood P - Aldosterone |
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Cortisol |
- produced in the adrenal cortex fasciculata & reticularis - must have an –OH @ C-11 of steroid core - plasma concentration is about 0.4 μmol w/ 96% bound to corticosteroid-binding globulin (CBG) - free ~ biologically active |
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Cortisol synthesis pwy |
Cholesterol ->> 17-hydroxyprogesterone -> 21β-hydroxylase (cytochrome P450)-> 11-deoxycortisol |
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Cortisol synthesis/secretion endocrine control |
Stressors -> CRH -> ACTH -> cortisol -| hypothalamus, pituitary (-fb) |
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CAH (Congenital Adrenal Hyperplasia) |
- deficiency in biosynthetic enzymes (21β-hydroxylase) -> synthesis diverts to DHEA & androstenedione -> masculinization, sexual precocity, accelerated linear growth - no -fb -> high ACTH -> adrenal hypertrophy -> excess androgens |
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Mechanism of ACTH action |
R: MC2R (melanocortin type 2 R) = GPCR [G(s)] -> AC -> cAMP -> IP3 (from ER) & DAG -> PKC -> steroid synthesis |
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Mechanism of Cortisol Action |
-> GR (glucocorticoid R in cyto) -> nucleus => TF -> GRE - metabolic effects: --> gluconeogenesis & glycogenolysis, -| peripheral glucose uptake --> lipolysis in adipocytes => ↑ circulating lipids; chronicly ↑ appetite & body fat redistribution --> muscle protein breakdown (chronically high cortisol lvls) -| cytokines -> anti-inflammatory & immunosuppressive -> osteoclast # & bone resporption, ↓ Ca intake & reabsoption => ↓ bone mass, wound healing; ↓ ECM & fibroblast P synthesis -> CNS: insomnia, hyperactivity, ↑ appetite, impairs memory |
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Addison's Disease |
- Adrenal insufficiency: 1° - due to destruction of adrenal cortex 2° - inadequate ACTH secretion (pituitary) 3° - inadequate CRH secretion (hypothalamus) - hyperpigmentation (↓-fb -> ↑POMC -> ACTH/MSH), weakness/fatigue, hypotension, weight loss, nausea & vomiting, loss of appetite, fasting hypoglycemia, muscle & joint pain |
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Cushing's Syndrome |
= hypercortisolism -> hyperplasia ACTH-dependent - due to ACTH (& CRH) hypersecretion ACTH-independent - due to adrenal tumor/excessive steroid administration - truncal obesity, moon face, buffalo hump, abdominal striae, osteoporosis, hypertension, bruising & poor wound healing, glucose intolerance/diabetes, psychosis, infections, hirsutism |
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Aldosterone |
- Produced in zona glomerulosa of adrenal cortex - 100x less than cortisol - Promotes Na retention & K secretion - 0.1-0.3 nM in blood (free, low affinity to albumin) - half-life 30 min |
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Aldosterone synthesis |
Corticosterone -> Aldosterone synthase -> aldosterone |
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Aldosterone action |
- CD: ↑ Na, ↓ K & H reabsorption - neonates: Na absorption in colon - sweat glands: regulate salt balance - taste buds & brain: regulate salt intake |
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Endocrine control of aldosteron synthesis & secretion |
- Renin/Angiotensin from kidney -> ↑ - Plasma K lvls: -fb (↑K -> ↑aldosterone) - HPA axis - minor role |
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Mechanism of aldosterone action |
-> MR (cyto mineralocorticoid R) -> nucleus -> TF - same affinity to cortisol, but: cortisol <-> 11HSD2 (11β-hydroxysteroid dehydrogenase 2) <-> cortisone (inactive) - spinorolactone = competitive R antagonist |
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11HSD2 deficiency |
= AME (apparent mineralocorticoid excess) - licorice -| 11HSD2 => MR activated by cortisol -> ↑ BP, ↑ Na, ↓ K, ↓ renin, ↓ aldosterone, ↑ urinary r(cortisol/cortisone) |
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Hypoaldosteronism |
↓ BP, ↑ K, ↓ Na - Addison's disease - combined mineralo- & gluco- deficiency due to adrenal cortex destruction - isolated: defect of aldosterone synthase - pseudohypoaldosteronism - mutation of Na channel genes/MR -> ↑ aldosterone (!), ↑ Na wasting |
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(Hyper)Aldosteronism |
↑ BP, ↑ aldosterone, ↓ K, ↓ renin - PA (1°) - 75% due to adrenal adenoma/bilateral adrenal hyperplasia (Conn syndrome) - 2° - edema in: congestive heart failure, liver cirrhosis, nephrotic syndrome: ↓ BV -> RAAS |
