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Sympathetic Nervous System

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					            Adrenal Medulla &
         Sympathetic Nervous System
Porterfield Chapter pp 131-137

Outline
     Anatomy
     Catecholamines
     Adrenal Medulla and Sympathetic Nervous System
     Catecholamine Synthesis
     Adrenergic Receptor Subtypes
     Regulation of Release
     Physiological Effects
     Pathophysiology
     Comparison – Sympathoadrenal and Sympathetic Nervous
     System




                             1
Overview
   Sympathetic Nervous System
– Adrenergic branch of autonomic nervous system
– First line of defense in responding to stress
   – Two branches
• 1) SNS - preganglionic cholinergic nerve endings synapse with
postganglionic adrenergic neurons
• 2) Sympathoadrenal System - preganglionic cholinergic nerve
endings synapse with postganglionic chromaffin cells (located in
adrenal medulla).
   Sympathetic response
– Extremely rapidly activated
– Responds to wide variety of stressors
– Uniquely tailored
• Individual components of both branches can be recruited singly
or in any combination.


Anatomy of the adrenal gland




Catecholamines
– Epinephrine and Norepinehrine &Dopamine (very little)

                               2
– Site of epinephrine synthesis:
– Adrenal medulla
– Chromaffin cells (neuroendocrine cells)
– Epinephrine:
– Adrenal medulla - sole source of epinephrine in circulation
– 85% of medullary output
– Hydrophilic
Catecholamines in circulation (hydrophilic)
EPINEPHRINE                          NOREPINEPHRINE
All from adrenal medulla             Most from sympathetic
                                     nerve

Approx 50% bound to                  Approx 50% bound to
albumin                              albumin

Levels = 20-50 ng/ml                 100-350 ng/ml
t½ < 10 seconds                      t½ < 15 seconds
SNS and adrenal medulla innervation




                                 3
Synthesis of catecholamines
Chromaffin cell




Catecholamine Synthesis:
– Tyrosine hydroxylase
– Rate limiting step
– All intermediate products       negative feedback on tyrosine
hydroxylase
– PNMT: Only in CNS and adrenal medulla
– Required for synthesis of epinephrine

Sympathetic Response
– J. Tepperman - “The sympathetic nervous system and adrenal
  medulla respond to differing physiological challenges by
  selective recruitment of subsystems as determined by site of
  release and receptor availability---
– All 88 keys on a piano are not struck at once; rather chords
  appropriate to the musical piece are played.”


Adrenergic Receptor Subtypes


                               4
Adrenergic Receptor Types (in general)
– Alpha
– Mostly mediated by NE (from SNS nerve endings)
– Constrictive events
– Excitatory events
– Beta
– Mostly mediated by E (from adrenal medulla)
– Dilatory events
– Relaxation events

Regulation of Release Sympathetic, Cholinergic Stimulus
– 1) Decreased blood pressure:
– In hemorrhage (need blood pressure stability)
– 2) Decreased blood glucose:                      NE & E
– Need energy mobilization
– 3) Decreased oxygen availability:
– Need + bronchodilation

4) Stress / Anxiety: (E/NE)

                              5
– Need + energy, + cardiac output, +blood to essential tissues
– 5) Cold:
– Need to + metabolism to conserve heat
6) Exercise:                                                      E
– Need to + oxygen and + blood to muscle,
+ energy mobilization
– 7) Postural hypotension:
– Need to + cardiac output when standing
Physiological Effects
“Fight or Flight”
The sympathetic response involves 〈and ® receptors working in
concert to increase delivery of O2 and energy sources to critical
body compartments for mobilization of energy.
   Sympathetic Response “Fight or Flight”
Tissue Direct           Response              Physiological
                                              Outcome
Lungs                   ↑ respiration         ↑O 2 to heart

Heart                  ↑ cardiac               ↑ blood/O 2
                       output                  to tissues
Vascular               +/- regional            Preferential shunting
Smooth                 blood flow              of
Muscle                                         blood
Skeletal               ↑ contraction           ↑ locomotion
Muscle

Liver                  ↑glycogenolysis         ↑ glucose to
                                                      tissues


Adipose Tissue         ↑ lipolysis             ↑FFA to tissues




                                  6
〈/® Receptors
Cardiovascular System
   ®1 Receptors
– Cardiac muscle contr. ↑ Cardiac output
   〈1/〈2 Receptors
– Vasoconstriction ↑ Peripheral resist.
* Skin, kidney, mucosa, G.I. tract
   ®2 Receptors
– vasodilation −− Peripheral resist.
* Heart, skeletal muscle, bronchial smooth muscle
* blood pressure = no change
α/β Receptors Working Together
   Specialized Smooth Muscle - Urinary Bladder
  β2 Receptor
– Non-sphincteric muscle
– Relaxation
 α2 Receptor
– Sphincter muscle
– Constriction


  Pathophysiology :Adrenal Medulla
   Hyposecretion
 – Not a serious physiological problem
– SNS compensates for cardiovascular regulation
– Other counter-regulatory hormones compensate for metabolic
effects
• Glucagon, GH, cortisol

Pathophysiology: Adrenal Medulla
   Hypersecretion - ↑ ↑ E/NE
– Pheochromocytoma - beign tumor (fatal if untreated because of
symptoms)

                                   7
• Severe hypertension
• Paroxysmal episodes – tachycardia, anxiety, headache, tremor,
sweating
• Severe damage to vascular cells (↑ ↑ Ca2+)
– Neuroblastoma – malignant tumor
• Same symptoms as above only more severe




Study questions:

   1- Identify the chemical nature and mechanism of action of catecholamines and their
      metabolic fate?
   2- Describe the biologic consequences of adrenal medullary activation and identify
      the target organs or tissues for catecholamine effects along with the receptor
      subtype that mediates the responses?
   3- Identify diseases caused by oversecretion of adrenal catechoamines?




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posted:8/30/2011
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