Regulation of Adrenal Function II Flashcards
Synthesis of Epinephrine f/ Tyrosine
Tyrosine (Tyr Hyd) -> L-Dopa (AA Decarb) -> Dopamine (Dop-B-hyd) -> NE (PNMT) -> EP
How does NE exit chromaffin granules?
Via VMAT in reverse mode
How do NE + EP get metabolized + excreted?
Phase I Oxidation (MAO)
Phase II Conjugation (COMT)
End product Vanillylmandelic Acid is excreted
What is responsible for orthostatic hypertension in pheocromocytoma?
Tx?
Downregulation of post-synaptic alpha receptors from continuous NE stimulation
Labetalol (Mixed blockers)
NE Receptor Binding
- Equal alpha
- B1»_space;» B2/3
EP Receptor binding
- Equal Alpha
- B1 = B2,3
- **Much more potent at B2
Alpha 1 Cellular Mech and Location
- Mech: Gq -> PLC/IP3. INC Ca++
- Locations: Vascular Smooth muscle, Liver, GU
Alpha 2 Mech + Location
Mech: Gi -> DEC cAMP, Opens K+ Channels
Location: Platelets, Presynaptic Nerve terminals on vascular smooth muscle; Pancreatic beta cells
Beta 1 Mech + Location
Mech: Gs -> INC cAMP
Location: Heart, Kidney, Adipocytes
Beta 2 Mech + Location
Mech: Gs -> INC cAMP
Location: Smooth muscle; Liver; SKM
Beta 3 Mech + Location
Mech: Gs -> INC cAMP
Location: Adipose; GI, Heart
Major effects of NE/EP at different receptors
a1: Vasoconstriction -> INC PVR + BP; mydriasis; closure of sphinncters
a2: inhibition of NE release; inhibition ACh; Inhibits insulin
B1: INC HR; INC Ionotrophy; INC Renin; INC Lipolysis
B3: INC Lipolysis
Additional effects of EP over NE
B2: Vasodilation + Bronchodilation; Tocolytic; Slight DEC PVR; Glycogenolysis, GNG in liver; Glycogenolysis in SKM; Glucagon Release; INC K+ Uptrake in SKM
What affect does Cortisol have on adrenal medulla
Induces PMNT -> Conversion of NE -> EP
Permissive nature/function cortisol
- Induce PMNT
- Promote a/B expression
- > Bronchodilation, glycogenolysis, Lipolysis. + vasoconstriction
What is the major vascular effect of low or absent cortisol?
Drop in BP
What neural signal initaites the secretion of Renin?
Baroreceptor reflex -> sympathetic ANS -> NE binds B1 on JGA -> Renin release + RAAS activation
Four factors that are sensed in kidney to secrete Renin
- DEC Plasma Volume
- DEC Afferent Arteriole pressure
- DEC Tubular NaCl
- INC SNS
3 secretagogues of Aldosterone
Level of control?
- ACTH
- Ang II
- INC K+
ACTH has weak effects
Ang II + K+ have potent effect
Mech Ang II + K+ effects on aldosterone
- Ang II binds AT1R -> Gq -> IP3 + INC Ca++
- High K+ depolarizes membrane potential -> Ca Influx
Ca Influx:
- stimulate SCC/Chol Desmolase
- Stimulate Aldosterone synthase
Cellular effects Aldosterone
LAte distal tubule/Principal cells collecting duct:
- INC ENaC
- INC Na/K ATPase
- INC ROMK
a-Intercalated:
- INC H+/K+ ATPase activity
- Reabsorb HCO3-
What is the risk of loss of aldosterone?
- Hyperkalemia, weakness/arrhythmia, hyponatremia, hypotension, + Shock
***Death within 2-3 Days
Chemicals w/ mineralocorticoid mimicry
- DOC
- Corticosterone
- 9a-fluorocortisol
- Cortisol
- Cortisone
Conn’s Syndrome
- S/S
- Tx
- Primary Hyperaldosteronism
- S/S: Hypernatremia, Hypokalemia, Metabolic alkalosis, HTN
- Tx: Surgical removal; K+ supplement; Spironolactone
