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19 Cards in this Set
- Front
- Back
What's the HPA axis?
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CRH --> Pit --> ACTH --> blood --> adrenal --> cortisol
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Adrenal Gland:
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salt (G), sugar (F), sex (R)
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Discuss action of Aldosterone (diagram):
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Salt: Regulated by Aldosterone
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Discuss action of Aldosterone (words):
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Classic presentation of aldosterone deficiency:
What would you want to measure? |
-Low Na and high K
-measure renin |
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How is cortisol regulated (diagram)?
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What all does cortisol do?
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*Cortisol Regulation
1. Hypothalamus-CRF (CRH) 2. Pituitary-ACTH (Corticotropin) 3. Adrenal- Cortisol is major negative regulator 4. Circadian rhythm, stress *Cortisol Function: sugar 1. Metabolism of carbohydrates, protein, fat 2. Vital Response to Stress (high levels compete with aldosterone in the kidney; it's also catabolic to provide energy) 3. Controls Inflammation (we use this in immune suppression) |
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Cortisol Synthesis (words):
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*CRF increases synthesis of Pro-opiomelanocortin (POMC); ACTH is cleaved from POMC
*Vasopressin (AVP) amplifies secretion of ACTH *ACTH activates its G-protein coupled receptor to increase cholesterol transport and conversion to pregnenolone via cholesterol desmolase *ACTH stimulates cortisol secretion (8-25 mg/day) |
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Cortisol Synthesis (diagram):
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Adrenal Steroid Biosynthesis:
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Glomerulosa: aldosterone
Fasciculata: Cortisol Reticularis: DHEAS |
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Cortisol action and metabolism:
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*Action:
-Peak cortisol is ~6 am, nadir is ~12 midnight -90% cortisol circulates bound to cortisol binding globulin (75%) and albumin (15%) prolonging t½ -Free cortisol (10% total) diffuses into cells, activates its nuclear receptor to affect transcription *Metabolism: -tissue 11ß Hydroxysteroid dehydrogenase isozymes inactivate cortisol to cortisone (kidney: HSD-2) and activate cortisone to cortisol (liver, adipose tissue: HSD-1) -conjugated in liver to glucuronic acid; excreted in bile |
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Circadian rhythm of Cortisol:
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Mechanisms of Cortisol Regulation:
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*Circadian rhythm
-Increases during sleep, declines during the day -Disturbed by illness, depression, CNS disorders, liver disease, renal failure, etc *Stress responsiveness -Originates in CNS (hypothalamus) via CRH -ACTH/cortisol secreted within minutes *Feedback inhibition -Fast feedback- rate of increase -Delayed feedback- time and dose dependent |
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Major Functions of Cortisol:
metabolic circulatory immune SNS CNS |
*Metabolic:
-increases supply of glucose “Glucocorticoid” -decreases sensitivity to insulin -inhibits amino acid utilization -increases lipolysis, gluconeogenesis *Circulatory: -maintains capillary integrity and vascular tone -increases number of alpha receptors (so they can bind NE and increase BP) *Immune: mobilization/function of leukocytes *SNS: required for epinephrine synthesis (adrenal medulla) *CNS: regulates appetite, euphoria, sleep |
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Major Functions of Adrenal Androgens:
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*DHEAS is the major adrenal androgen
*Androstenedione is converted to Testosterone (and E2): regulates libido and adrenarche *Adrenarche: differentiation of sweat glands and terminal hair (pubic and axillary) at puberty *Regulation is poorly understood: ACTH has a role, but other pituitary factors may be involved *Androstenedione accounts for 5% Testosterone in men, 40-60% in women |
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Flow chart of NE/E synthesis in adrenal medulla:
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Synthetic pathway of NE/E:
how are metabolite levels useful? |
*metabolites can be used to give an indirect measure of the amount of NE/E being made
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Describe the Adrenal Medulla as an extension of the SNS:
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*Peripheral nerves: NE is locally produced and acts as neurotransmitter
*Medulla: modified sympathetic ganglion, 80% of catecholamine production is E: “flight or fight” *Effects of E, NE mediated by alpha and ß receptors: -alpha receptors: alpha1 post-synaptic (vessels, smooth muscle, pupils): NE>E; alpha2 presynaptic sympathetic nerves: NE:E -ßreceptors: ß1 heart: NE:E; ß2 vessels, bronchi, uterus, liver, muscle: E>>NE; ß3 adipose, GI -Cardiovascular, smooth muscle and metabolic actions |
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Adrenal Insufficiency:
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ALD (Adrenoleukodystrophy- X linked)
Impaired steroidogenesis *these are the ones she mentioned |