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DAVANGERE.
DEPT OF ANESTHESIA
PHYSIOLOGY OF AUTONOMIC
NERVOUS SYSTEM
CHAIRPERSON
Dr RAMAPPA M.D
READER
DATE: 20-08-2010
PRESENTED BY
Dr PRITAM
Post Graduate
1
INTRODUCTION
Much of the action of the body in maintaining,
cardiovascular, gastrointestinal and thermal
homeostasis occurs through the autonomic
nervous system (ANS).
The ANS is our primary defense against
challenges, to maintain homeostasis. It
provides involuntary control and organization
of both maintenance and stress responses.
2
HISTORY
GALEN - spoke of sympathy
& consent of body & was
probably 1st to describe
Paravertebral nerve trunks.
THOMAS WILLIS
notion of
involuntary
movements
3
ROBERT WHYTT
recognized that adequate
stimulation is necessary for
visceral sensation & that all
sympathy must be referred
to brain
JACOB WINSLOW
COINED TERM SYMPATHETIC
CLAUDE BERNARD
i) Theory of chemical synapse
transmission.
ii) Described fundamental role
of ANS in maintaining
Homeostasis (la fixite du
milieu interior)
BROWN-SEQUARD
noted that sympathetic
stimulation constricts blood
vessels.
WALTER GASKELL
described white
communicanti rami &
recognized that the system
contained 2 antagonist set
of nerve fibers.
6
JOHN LANGLEY
i) Mapped 3 distinct divisions in
system.
ii) Coined term AUTONOMIC &
declared that
it was largely independent from
brain.
SHERRINGTON
initiated systemic study of
reflexes & described
Characteristics of reflex
function.
7
JJ ABEL
synthetized
Epinephrine
DEFINITION
It is network of nerves & ganglia that
controls involuntary physiologic
parameters & maintains internal
homeostasis & stress responses.
It is primarily peripheral efferent system.
Autonomic - self governing
9
PURPOSE OF AUTONOMIC
NERVOUS SYSTEM
A major goal of anesthetic administration is
maintaining optimum homeostasis in the patient.
The intelligent administration of anesthetic
care to patients requires knowledge of ANS
pharmacology in order to achieve desirable
interactions of anesthetics with the involuntary
control system and to avoid responses or
interactions with deleterious effects.
10
FUNCTIONAL ANATOMY
Nervous System
Central Nervous
System
Peripheral
Nervous System
Somatic
Sympathetic
Parasympathetic
Autonomic
Enteric
Nervous
System
11
Difference between
Somatic
Autonomic
Organ supplied
Skeletal muscles
Within CNS
Nerve fibers
Myelinated
Preganglionic - myelinated
Postganglionic- nonmyelinated
Peripheral plexus
Absent
Present
Efferent transmitter
ACH
ACH, Nor-adrenaline
Activity maintained, no
formation
on organ supplied
Atrophy
12
13
14
16
18
Terminal/Collateral ganglia
Small, few in no. & near
their target organs.
E.g Adrenal medulla
20
PARASYMPATHETIC NERVOUS
SYSTEM
21
22
Glossopharyngeal
nerve synapses in
the Otic ganglion.
These post
ganglionic fibres
innervate the
parotid, salivary
and lacrimal glands.
24
25
26
27
Difference between
Sympathetic
Origin
Parasympathetic
Craniosacral (III, VII, IX, X,
S2-S4)
Distribution
Wide
Ganglia
Post-ganglionic fibre
Long
Short
1:20 to 1:100
ratio
Transmitter
plexus
Nor-adrenaline (major)
ACH
Acetylcholine (minor)
Stability of transmitter
Imp. Function
Tackling
Assimilation of food,
stress
and emergency
conservation of energy
28
29
30
It contains
Myenteric /Auerbach plexus
Submucous /Meissner plexus.
Acetylcholine is principle excitatory trigger of nonspecific portion of ENS. It causes muscle contraction.
Role of cholinergic neurons are Excitation of
external muscles, activation of motor neurons
augmenting secretion of water & electrolytes &
stimulation of gastric cells.
Nicotinic antagonist causes abolition of enteric
reflexes while cholinergic overload or over-reversal of
muscle relaxant causes hyper-reactive enteric reflexes.
31
FUNCTIONS OF ANS
Sympathetic
Fight or flight
E division
Exercise, excitement,
emergency, and embarrassment
Parasympathetic
Rest and digest
D division
Digestion, defecation, and
diuresis
32
Antagonist
ic Control
Most internal organs are
innervated by both
branches of the ANS which
exhibit antagonistic control
AUTONOMIC INNERVATION
Heart:
The heart is well supplied by SNS
and PNS. These nerves affect
cardiac pumping is 3 ways -
37
Peripheral circulation :
SNS nerves are imp regulators of the peripheral
circulation stimulation produces both vasodilatation &
vasoconstriction with vasoconstriction effect being
predominant.
Blood vessels in the skin, kidney, spleen and mesentery
have a extensive SNS distribution where as those in the
heart, brain and muscle have less SNS innervation.
Basal vasomotor tone is maintained by impulses from the
lateral portion of the vasomotor center in the medulla
oblongata that continuously transmits impulses through
SNS maintaining partial arteriolar and venular constriction.
38
Lungs :
Lungs are innervated
by both SNS and PNS.
Postganglionic SNS
fibres from upper
thoracic ganglia
(stellate) pass to the
lungs to innervate the
smooth muscles of the
bronchi and pulmonary
blood vessels.
PNS innervation of
these structures is
from the vagus nerve.
39
40
ANS Neurotransmitters
Predominant SNS neurotransmitter-nor
epinephrine.
Predominant PNS neurotransmitterAch.
41
42
Catecholamines
A catecholamine is any compound having a catechol nucleus (a
benzene ring with 2 adjacent OH group) and an amine
containing side.
Endogenous catecholamines in humans are dopamine, NE and
EPI.
Dopamine is a neurotransmitter in CNS and primarily involved
in co-ordinating motor activity in the brain. It is a precursor
of NE. NE is synthesized and stored in the nerve endings of
postganglionic SNS neurons.
Catecholamines are often referred to as adrenergic drugs
because their effector action is mediated through receptors
specific for the SNS.
43
44
Regulation :
Increased SNS activity as in chronic stress stimulates
the synthesis of tyrosine hydroxylase & dopamine
hydroxylase.
Glucocorticoid from the adrenal cortex pass through
the adrenal medulla and stimulate increase in
phenylethanolamine N methyl transferase that
methylates NE to EPI.
The release of NE is dependent upon depolarization of
the nerve and an increase calcium ion permeability. NE
inhibits its own release by stimulating presynaptic
prejunctional alpha 2 receptors.
45
Inactivation :
Catcholamine are removed from the synaptic cleft by 3
mechanism.
These are
RECEPTORS
48
Cholinergic receptors
Cholinergic
receptors
Nicotinic
NM
NN
Muscarinic
M1
M2
M3
M4
M5
49
Nicotinic receptors
Pentamers of 5 types of
glycoprotein subunits:
(a1-a10), (b2-b5), , & .
Each subunit has 4
hydrophobic helical
membrane-spanning
domains labeled M1-M4.
The M2 regions, which
contain rings of negatively
charged a.a & leucine
residues, form the pore
walls & provide hydrophilic
environment for ions.
50
51
Muscarinic receptors
These are 7 transmembrane domain, Gprotein coupled receptors.
M1, M3,& M5
52
Muscarinic receptors
M2 & M4
53
54
55
56
Adrenergic Receptors
Adrenerg
ic
receptor
s
receptor
s
receptor
s
57
1 Adrenergic receptor
G protein-coupled receptor (GPCR) associated with the
Gq heterotrimeric G-protein .
It consists of 3 highly homologous subtypes, including
1A, 1B, and 1Dadrenergic
58
2 Adrenergic receptor
59
Adrenergic receptor
It is a G-protein coupled receptor associated
with the Gs heterotrimeric G-protein.
They are further divided into 1,2 & 3.
60
61
62
RECEPTORS IN
CARDIOVASCULAR SYSTEM
Coronary arteries :
Sympathetic nerves cause coronary
vasoconstriction which is mediated by
postsynaptic 2 receptors.
Larger epicardial arteries posses mainly
1 receptors (1 agonists have got little
influence on coronary resistance).
63
Myocardium :
Myocardial postsynaptic 1 receptors mediate perhaps as
much as 30-50% of the basal ionotrophic tone of the
normal heart.
The increase in density of myocardial 1 adrenoreceptors
shows a relative increase in failure and myocardial
ischaemia, thus enhancing of myocardial 1 receptor
numbers and sensitivity
Intracellular mobilization of cytosolic calcium by the
activated 1 myocardial receptor during ischemia appears
to contribute to arrhythmias. The 1 receptor also
increases the sensitivity of contractile elements to calcium.
64
-PERIPHERAL VESSELS
Activation of presynaptic 2 vascular receptor inhibit
NE release, produces vasodilatation.
Whereas postsynaptic 1 and 2 vascular receptors
subserve vasoconstriction.
Postsynaptic 1 and 2 receptors co-exist in both the
arterial and venous sides of the circulation with
relative distribution of 2 receptors being greater on
the venous side.
Nor epinephrine is the most potent venoconstrictor of
all the catecholamine
65
-RECEPTORS IN CNS
There is a close association between and
for BP and HR control.
Cerebral and Spinal cord presynpatic 2
receptors also involved in inhibition of
presynpatic NE release.
Central neuraxial injection of 2 agonists such
as clonidine act at these sites to produce
analgesia, sedation and CVS depression
66
-receptors in CVS
1 and 2 receptors are present in myocardium & are functionally
coupled to adenyl cyclase.
Post synaptic 1 receptors are distributed predominantly to myocardium
in SA node and ventricular conduction system.
2 receptors have the same distribution but are presynaptic. Activation
of 2 presynaptic receptors accelerates the release of NE into the
synaptic cleft.
The effect of NE on ionotropism in the normal heart is mediated
entirely through the postsynaptic 1 receptors whereas the ionotropic
effects of EPI are mediated through both the 1 and 2 receptors.
2 receptors may also mediate the chronotrophic response to EPI
because selective 1 antagonists are less effective in suppressing
68
induced tachycardias than the non selective 1 antagonist propranolol.
-Peripheral vessels
Post synaptic vascular receptors are virtually
all of the 2 subtype.
The 2 receptors are located in the smooth
muscle of the blood vessels of the skin, muscle,
mesentery and bronchi.
Stimulation of post synaptic 2 receptors
produces vasodilatation and bronchial
relaxation.
69
DOPAMINERGIC
RECEPTORS
Dopaminer
gic
Receptors
DA1
Postsynapti
c
DA2
Presynapti
c
Postsynapti
c
71
Peripheral vessels
Greatest numbers of DA1-postsynaptic receptors are found
on vascular smooth muscle cells of the kidney and
mesentery.
The vascular receptors are like the 2 receptors linked to
adenyl-cyclase and mediate smooth muscle relaxation.
Activation of these receptors produces vasodilatation
increasing blood flow to the organs. Concurrent activation
of vascular presynaptic DA2 receptors also inhibits NE
release at the presynaptic 2 receptors.
Higher doses of dopamine can mediate vasoconstriction via
the postsynaptic 1 and 2 receptors.
72
73
FUNCTIONAL RESPONSE
MEDIATED BY ANS
76
Effector
organ
Adrenergic
response
Receptor
Cholinergic
response
Receptor
Rate of
Contraction
Increase
Decrease
M2
Force of
Contraction
Increase
Decrease
M2
Bronchodila
tation
Bronchocon
striction
M3
HEART
LUNG
Bronchiolar
smooth
muscle
77
Effector
organ
Adrenergic
response
Arteries
(most)
Vasoconstriction 1
Veins
Vasoconstriction 1
Skeletal
muscle
Vasodilatation
Endothelium
Receptor
Cholinergic
response
Receptor
Release
EDRF
M3
78
Effector
organ
Adrenergi Receptor
c
response
Cholinergi Receptor
c
response
Baldder
wall
Relaxation
Contraction
M3
Ureter
Contraction
Relaxation
M3
Sphincter
Contraction
Relaxation
M3
Uterus
(pregnant)
Relaxation
Contraction
2
1
Variable
M3
Penis/Vas
deferens
Ejaculation
Erection
M3
79
Effector
organ
Adrenergic
response
Receptor
Cholinergic
response
Receptor
Increase
secretion
Increased
secretion
M3
Relaxation
Contraction
22
1
Contraction
Relaxation
M3
M3
Increase
secretion
M3
Gastro-Intestinal tract
Glands
Smooth
muscle
Walls
Sphincters
Secretions
80
Effector organ
Adrenergic
response
Receptor
Cholinergic
response
Receptor
------
------
Increased
secretion
M3
SKIN
Hair follicles
Smooth muscles
Contraction
Piloerection
Thermoregulation
------
---------
Apocrine (stress)
Increased
secretion
SWEAT GLANDS
81
Effector
organ
Adrenergic
response
Receptor
Cholinergic
response
Receptor
EYE
Iris
Radial muscle
Circular
muscle
Contraction
----------
1
-----
-----------Contraction
M3
Ciliary muscle
Relaxation
Contraction
M3
Ciliary
epithelium
secretion of
Aqueous
Humour
---------
82
AUTONOMIC REFLEXES
DURING ANAESTHESIA
AND SURGERY
83
Afferent
Center
Efferent
Vagus n.
Effects
Sinus
bradycardia,
Cardiac
Dysrhythmias,
Ventricular
84
Glossopharyngeal n.
Center
Efferent
Vagus n.
Effect
BP & HR
85
NASOCARDIAC REFLEX
Stimulus
Afferent
Maxillary
&
Ethmoidal
division
of
Trigeminal n.
Center
Brainstem nuclei.
Efferent
Vagus n.
Effect
BP & HR.
86
PHARYNGEAL REFLEX
Stimulus
Afferent
Glossopharyngeal
Efferent
Vagus
Effect
87
Afferent
Center
Efferent
Effect
88
Stimulus
Afferent
Vagus
Center
Efferent
Vagus
Effect
89
ABDOMINAL REFLEX
Stimulus
Afferent
Splanchnic nerves
Efferent
Vagus
Effect
Peritoneal, mesenteric reflex, & celiac plexus reflex have same effects.
90
AUTONOMIC
DYSFUNCTION
91
93
Afferent
Central
Efferent
Response
96
Afferent
Center
Efferent
Vagus
Response
After standing
HR
Exercise,
reflex/withdrawl
of
parasympathetic
tone.
Approx 15sec later
HR
At approx 30 sec
Relative bradycardia
Stimulus
Afferent
Center
Efferent
Vagus
Response
100
102
Stimulus
Afferent
Center
Nucleus
Tractus
Solitarus,
Rostral
ventrolateral
medulla,
Hypothalamus.
Efferent
Sympathetic vasomotor
Response
105
106
DISEASES ASSOCIATED
WITH PROGRESSIVE
NEUROLOGICAL
IMPAIRMENT OF
AUTONOMIC NERVOUS
SYSTEM
107
Neurological diseases
Tabes Dorsalis
Syringomyelia
Amyloidosis
109
Ageing
Approximately 20% of people over 65 years of age have
postural hypotension.
Half of these patients are symptomatic i.e they
experience dizziness, faintness or loss of consciousness.
It is well known that the reflex regulation of heart rate
which is mediated primarily by parasympathetic
mechanisms declines progressively with age.
There will be a selective or earlier impairment of
parasympathetic function with aging with a minimal or a
more gradual involvement of the sympathetic nervous
system
110
Diabetes Mellitus
Diabetic autonomic neuropathy is a well known clinical entity.
It may result from neuronal degeneration or metabolically
related neuronal dysfunction.
The afferent central or efferent reflex pathways each can
be involved.
It has been suggested that the Vagal neuropathy occurs
earlier in the course of DM than the sympathetic neuropathy.
The most sensitive test of cardiac parasympathetic
impairment is that of determining RSA during forceful
breathing. Intolerance to upright posture is often evident.
The presence of symptomatic postural hypotension is
associated with a poor prognosis. These patients are prone to
sudden cardiac death.
111
REFERENCES
1.
2.
3.
4.
5.
6.
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