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19 Cards in this Set

  • Front
  • Back
What's the HPA axis?
CRH --> Pit --> ACTH --> blood --> adrenal --> cortisol
CRH --> Pit --> ACTH --> blood --> adrenal --> cortisol
Adrenal Gland:
salt (G), sugar (F), sex (R)
salt (G), sugar (F), sex (R)
Discuss action of Aldosterone (diagram):
Salt: Regulated by Aldosterone
Salt: Regulated by Aldosterone
Discuss action of Aldosterone (words):
Classic presentation of aldosterone deficiency:

What would you want to measure?
-Low Na and high K

-measure renin
How is cortisol regulated (diagram)?
What all does cortisol do?
*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)
Cortisol Synthesis (words):
*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)
Cortisol Synthesis (diagram):
Adrenal Steroid Biosynthesis:
Glomerulosa: aldosterone
Fasciculata: Cortisol
Reticularis: DHEAS
Cortisol action and metabolism:
*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
Circadian rhythm of Cortisol:
Mechanisms of Cortisol Regulation:
*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
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
Major Functions of Adrenal Androgens:
*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
Flow chart of NE/E synthesis in adrenal medulla:
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
Describe the Adrenal Medulla as an extension of the SNS:
*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
Adrenal Insufficiency :
ALD (Adrenoleukodystrophy- X linked)
Impaired steroidogenesis
*these are the ones she mentioned