Regulation of Adrenal Function II

Question 1

Synthesis of Epinephrine f/ Tyrosine

Answer 1

Tyrosine (Tyr Hyd) -> L-Dopa (AA Decarb) -> Dopamine (Dop-B-hyd) -> NE (PNMT) -> EP

Question 2

How does NE exit chromaffin granules?

Answer 2

Via VMAT in reverse mode

Question 3

How do NE + EP get metabolized + excreted?

Answer 3

Phase I Oxidation (MAO)
Phase II Conjugation (COMT)

End product Vanillylmandelic Acid is excreted

Question 4

What is responsible for orthostatic hypertension in pheocromocytoma?

Tx?

Answer 4

Downregulation of post-synaptic alpha receptors from continuous NE stimulation

Labetalol (Mixed blockers)

Question 5

NE Receptor Binding

Answer 5

• Equal alpha

- B1&raquo_space;» B2/3

Question 6

EP Receptor binding

Answer 6

• Equal Alpha
• B1 = B2,3
• **Much more potent at B2

Question 7

Alpha 1 Cellular Mech and Location

Answer 7

• Mech: Gq -> PLC/IP3. INC Ca++

- Locations: Vascular Smooth muscle, Liver, GU

Question 8

Alpha 2 Mech + Location

Answer 8

Mech: Gi -> DEC cAMP, Opens K+ Channels

Location: Platelets, Presynaptic Nerve terminals on vascular smooth muscle; Pancreatic beta cells

Question 9

Beta 1 Mech + Location

Answer 9

Mech: Gs -> INC cAMP

Location: Heart, Kidney, Adipocytes

Question 10

Beta 2 Mech + Location

Answer 10

Mech: Gs -> INC cAMP

Location: Smooth muscle; Liver; SKM

Question 11

Beta 3 Mech + Location

Answer 11

Mech: Gs -> INC cAMP

Location: Adipose; GI, Heart

Question 12

Major effects of NE/EP at different receptors

Answer 12

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

Question 13

Additional effects of EP over NE

Answer 13

B2: Vasodilation + Bronchodilation; Tocolytic; Slight DEC PVR; Glycogenolysis, GNG in liver; Glycogenolysis in SKM; Glucagon Release; INC K+ Uptrake in SKM

Question 14

What affect does Cortisol have on adrenal medulla

Answer 14

Induces PMNT -> Conversion of NE -> EP

Question 15

Permissive nature/function cortisol

Answer 15

• Induce PMNT
• Promote a/B expression
• > Bronchodilation, glycogenolysis, Lipolysis. + vasoconstriction

Question 16

What is the major vascular effect of low or absent cortisol?

Answer 16

Drop in BP

Question 17

What neural signal initaites the secretion of Renin?

Answer 17

Baroreceptor reflex -> sympathetic ANS -> NE binds B1 on JGA -> Renin release + RAAS activation

Question 18

Four factors that are sensed in kidney to secrete Renin

Answer 18

• DEC Plasma Volume
• DEC Afferent Arteriole pressure
• DEC Tubular NaCl
• INC SNS

Question 19

3 secretagogues of Aldosterone

Level of control?

Answer 19

• ACTH
• Ang II
• INC K+

ACTH has weak effects

Ang II + K+ have potent effect

Question 20

Mech Ang II + K+ effects on aldosterone

Answer 20

• Ang II binds AT1R -> Gq -> IP3 + INC Ca++
• High K+ depolarizes membrane potential -> Ca Influx

Ca Influx:

1. stimulate SCC/Chol Desmolase
2. Stimulate Aldosterone synthase

Question 21

Cellular effects Aldosterone

Answer 21

LAte distal tubule/Principal cells collecting duct:

• INC ENaC
• INC Na/K ATPase
• INC ROMK

a-Intercalated:

• INC H+/K+ ATPase activity
• Reabsorb HCO3-

Question 22

What is the risk of loss of aldosterone?

Answer 22

• Hyperkalemia, weakness/arrhythmia, hyponatremia, hypotension, + Shock

***Death within 2-3 Days

Question 23

Chemicals w/ mineralocorticoid mimicry

Answer 23

• DOC
• Corticosterone
• 9a-fluorocortisol
• Cortisol
• Cortisone

Question 24

Conn’s Syndrome

• S/S
• Tx

Answer 24

• Primary Hyperaldosteronism
• S/S: Hypernatremia, Hypokalemia, Metabolic alkalosis, HTN
• Tx: Surgical removal; K+ supplement; Spironolactone