Autonomic nervous

system
Dr Onyango K
3/2/2020
Objectives
 Importance in regulation of body functions.
 Functional specialization of sympathetic and
parasympathetic divisions.
 Differences in central connections and reflex
arc of somatic nervous system and ANS.
 Pre - and post-ganglionic fibers of sympathetic
and parasympathetic divisions of ANS.
 Name the common neurotransmitters in ANS
and their receptors.
 General organization of ANS at different
levels of the neuraxis.
Somatic vs autonomic NS
N-AChR Smoo
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Functions
Maintenance of homeostatic
conditions of the body.
Regulation of visceral activities.
Smoothening body’s responses to
environmental changes.
Coordination of body’s responses
to exercise and stress.
Assisting the endocrine system to
regulate reproductive functions.
Traditionally divided into two
subdivisions: sympathetic and
parasympathetic, based on their
anatomic, functional and
neurochemical properties.
Enteric nervous system is
considered to be the third
division of ANS.
The cell bodies of sympathetic system
are located in the thoracic and
abdominal segments of the spinal
cord and sympathetic ganglia are
present as a chain close to the
vertebral column.
This system is also termed as the
thoracolumbar division of the ANS for
the location of the ganglia and cell
bodies of neurons at thoracic and
lumbar segments of spinal cord.
The sympathetic system called
adrenergic for adrenaline (or
noradren­aline) like actions
resulting from sympathetic
activation; and the
parasympathetic system as
cholinergic for ace­tylcholine like
actions from parasympathetic
activation.
The sympathetic division is
primarily meant for utilization of
metabolic resources and
emergency responses of the
body, whereas the
parasympathetic divi­sion helps in
restoration and build-up of the
body’s reserves and the
elimination of waste products.
 Almost all the organs are supplied by
both sympathetic and parasympathetic
nerves and usually they are activated in a
reciprocal fashion.
When the dis­charge rate in one division is
increased, the rate in the other division is
decreased.
When sym­pathetic activation occurs
during exercise to increase heart rate,
simultaneous decreased vagal activity
also contributes to achieve the target
increase in heart rate.
In some organs, sympathetic and
parasympathetic systems work
synergistically.
 For example, to enhance
gastrointestinal secretions, when
parasympathetic stimulation
increases volume and enzyme
content, simultaneous
sympathetic activation
contributes to increased mucus
content of the secretory product.
Few structures such as blood
vessels and skin receive only
sympathetic innervation and
therefore, their functions are
regulated by alteration in the rate
of sympathetic discharge to these
structures.
Somatic vs Autonomic Nervous
System
The nervous system contacts all
organs and tissues of the body
via the sensory system (afferent
innervation), motor system
(efferent innervation) and the
ANS.
For efferent innervation of somatic
system (i.e. the motor pathway),
axons originate from cell body of
neurons in the motor cortex and
terminate directly or indirectly on
motor neurons in the ventral horn of
the spinal cord or in the brainstem
motor nuclei, and usually the second
order neuron (or sometimes the third
order neuron) innervates the skeletal
muscle.
In ANS, efferent pathway
consists of two or three-neuron
tract with one or two synapses
interposed between the center
and the effector cells.
The cell bodies of autonomic motor
neurons are located in the
intermediolateral horn of spinal cord or in
the specific brainstem cranial nerve
nuclei.
The efferent fiber emerges from CNS as
the preganglionic axon and then synapses
with the cell bod­ies of neurons located in
a peripheral ganglion.
The neuron from the ganglion then
projects as postganglionic axon to the
effector cells (usually a visceral organ).
Reflex arc
The somatic nervous system
collects information from the
external environment, whereas
the ANS collects informa­tion
usually from inside the body, i.e.
the changes in visceral
structures.
Receptors are located in the body
surface or in the muscu­loskeletal
system in somatic system.
 In ANS, the receptors are
present in the visceral structures.
Afferent pathway
The afferent neurons of somatic system
enter spinal cord via dorsal root with their
cell bodies in the dorsal root gan­glion and
terminate on interneurons in deeper
layers of dorsal horn or on motor neurons
in the ventral horn.
The afferent neurons of ANS enter spinal
cord in a similar fash­ion, but they
terminate on autonomic efferent neurons
having their cell bodies in
intermediolateral horn (ILH) of spinal
cord.
Central component in somatic system
consists of the cell body of a motor neuron
in the ventral horn of the spinal cord on
which the afferent neuron directly
terminates monosynaptically.
The afferent neuron may also contact
motor neuron through interneurons via
disynaptic or poly­synaptic connections.
In ANS, the cell bodies of central neurons
are located in intermediolateral horn of
spinal cord on which the affer­ent neuron
directly terminates.
Efferent pathway
The efferent neurons in somatic
system are motor neurons that
originate from ventral horn of
spinal cord and directly terminate
on effector organ, which is
usually a skeletal muscle.
There is a single efferent neuron
between the CNS and the effector
organ in somatic system.
In ANS, there are two neurons between
the CNS and the effector organ .
The first efferent neuron is the
preganglionic neuron that has cell body
in the intermediolateral horn of spi­nal
cord or in the cranial nerve nuclei in
brainstem.
The second efferent neuron is the
postganglionic neuron that has cell
body in the ganglia outside the spinal
cord or in the effector organ.
Somatic motor nerves innervate
skeletal muscles.
The efferent neurons of ANS
innervate visceral organs
(smooth muscle, cardiac muscle,
glandular tissues, etc.).
Efferent pathways in ANS
The preganglionic neurons leave spinal
cord via white rami communicantes to
the paravertebral sympathetic ganglion
where they contact cell bodies of
postgangli­onic neuron, the axons of
which terminate on effector organ.
The postganglionic sympathetic neurons
to head originate from superior and
middle cervical ganglia and stellate
ganglion.
These ganglia are in fact extension of
sympathetic ganglion chain into the neck.
Axons of preganglionic neurons
give collaterals to ter­minate on
another set of cell bodies in the
paraver­tebral ganglion chain.
Axons of these postganglionic
neurons enter gray rami
communicantes and from there
enter into the spinal nerve to
finally innervate the effector
organs.
Some of the preganglionic neurons do not
relay in paravertebral ganglion chain,
rather they come out directly of the
ganglion chain to terminate on the cell
bodies of postganglionic neurons located in
collateral ganglion that are present close to
the effector organ.
In this efferent pathway of sympathetic
system, the preganglionic fibers are longer
than the postganglionic fibers.
Thus, the postganglionic neurons in this
system form short noradrenergic neurons.
In parasympathetic system, the
preganglionic neurons of cranial part
originate from cell bodies in the cranial
nerve nuclei (III, VII, IX and X) in the
brainstem and terminate in the
postganglionic neuron located very close
to or in the visceral organ.
The preganglionic neurons of sacral part
follow a similar route except that the
fibers originate from cell bodies in the
intermediolateral horn of spinal cord and
traverse in spinal nerve.
In sympathetic system, the
preganglionic fibers are smaller
than the postganglionic fibers.
In parasympathetic system, the
preganglionic fibers are much
longer than the postganglionic
fibers .
NEUROTRANSMITTERS
In the somatic nervous system, the
efferent fibers terminate on motor end
plate usually with one axon terminal to
one skeletal muscle fiber.
The neurotransmitter is acetylcholine.
 In ANS, postganglionic axons
terminate in varicosities, the swellings
enriched in synaptic vesicles that
release the transmitter into the
extracellular space surround­ing the
effector cells.
The electrical activity for
discharge of autonomic fibers
originates in some of the effector
cells and then propa­gates to cells
of rest of the tissue via gap
junctions.
 The neurotransmitters in ANS
are acetylcholine, noradrenaline
and others.
ORGANIZATION OF ANS
Organization of ANS occurs at
five different levels: corti­cal
organization, hypothalamic
organization, brainstem
organization, spinal organization
and peripheral organiza­tion.
CORTICAL
Corticalareas controlling functions
of ANS are mainly limbic areas and
prefrontal cortex.
The sympathetic responses to
emotion originate in the limbic and
prefrontal cortical areas.
These areas activate sympathetic
system by stimulat­ing hypothalamic
and brainstem areas that have influ­
ence on the system.
HYPOTHALAMUS
Has considerable influence on
autonomic
Hypothalamo­pituitary axis con­
trols secretions of major
endocrine glands.
Receives collaterals from
ascending pathways, especially
from spinothalamic tracts that
transmit pain impulses.
Integrates somatosensory, endo­
crine and autonomic responses that
are essential components of
homeostatic mechanisms during
stressful situations like major
surgical procedures, exposures to
extreme weathers, trauma and
hemorrhage.
Hypothal­amus is the head-ganglion
of sympathetic nervous system.
Brainstem
Brainstem areas contain major
nuclei of ANS.
 These are broadly classified into
two categories: parasympathetic
nuclei and sympathetic nuclei.
The cranial outflow of
parasympathetic system
originates from cranial nerve
nuclei that are located in the
brain­stem.
The cranial nerves that carry
parasympathetic fibers are
oculomotor (III cranial nerve),
facial (VII cranial nerve),
glossopharyngeal (IX cranial
nerve) and vagus (X cranial
 Nucleus tractus solitarius (NTS) in the
medulla receives general visceral
sensation via IX and X cranial nerves.
It is also closely connected with
reticular formation containing cardio­
respiratory centers.
NTS mediates respiratory and
cardiovascular responses to autonomic
activation.
Special visceral sensations in VII, IX and
X cranial nerves reach NTS.
Edinger-Westphal nucleus in the
midbrain is the nucleus of III
cranial nerve.
Salivary nucleus is located in
pons and dorsal motor nucleus of
vagus in medulla.
Sympathetic fibers originate from
vasomotor center in the medulla and
project to the intermediolateral horn
of spi­nal cord via bulbospinal pathway.
Nucleus gigantocellularis and
parvocellularis in the reticular
formation on stimulation depress
activity of vasomotor center.
Stimulation of NTS inhibits
sympathetic outflow and stimulates
vagal activity.
Spinal
Cell bodies of autonomic efferent neurons are
located in the intermediolateral column of the
spinal cord.
Sympathetic Outflow Sympathetic fibers
originate from thoracic and lumbar segments
(T1 to L3) of spinal cord.
Sympathetic system is called thoracolumbar
outflow of ANS.
Spinal component of parasympathetic system
originates from sacral segments (S2 to S4) of
spinal cord.
For its cra­nial and sacral origin, parasympathetic
system is called craniosacral outflow of ANS.
Peripheral
Autonomic fibers from CNS reach visceral
cranial nerves and somatic nerves.
They are distributed to target organs via
various ganglions .
The gan­glia of sympathetic system are
close to spinal cord and the ganglia of
parasympathetic system are close to the
organs.
There are two sets of neurons in the
efferent pathway: preganglionic and
postganglionic neurons.
Receptors ANS
Receptors for acetylcholine
A. Nicotinic receptors
 Postganglionic neurons in the autonomic ganglia
 Neuromuscular junctions of skeletal muscle
 Some CNS neurons

B. Muscarinic receptors
 Smooth muscle
 Cardiac muscle
 Gland cells
 Some CNS neurons
 Some neurons of autonomic ganglia (although
the great majority of receptors at this site are
nicotinic)
II. Receptors for norepinephrine
and epinephrine
Smooth muscle
Cardiac muscle
Gland cells
Other tissue cells (e.g., adipose,
bone, renal tubules)
Some CNS neurons
Preganglionic neurons of
sympathetic system originate
from intermediolateral horn of
thoracolumbar segments of
spinal cord.
They terminate in sympathetic
chain of ganglion from where
postganglionic fibers originate
and innervate the viscera.
In sympathetic system,
preganglionic neurons are shorter
than postganglionic neurons.
Preganglionic neurons of
parasympathetic system
originate from cranial nerve
nuclei in brainstem and
intermediolat­eral horn of sacral
segments of spinal cord.
In sympathetic system,
postganglionic fibers originate
from sympathetic chain of
ganglia and terminate in the
viscera.
In parasympathetic system,
postganglionic fibers are located
close to or in the effector organs.
Postganglionic parasympathetic
fibers are very small.
Effectsare mediated by release
of noradrenaline from
sympathetic nerve endings and
adrenaline from adrenal medulla.
EFFECTS OF SYMPATHETIC
STIMULATION
Catecholamines elicit their effects
by acting on adrenergic receptors.
Adrenergic receptors are broadly
divided into two types: α and β.
The α receptor has two subtypes: α1
and α2; and β receptor has three
subtypes: β1, β2, and β3.
Generally, β receptors are more
sensitive to adrenaline and α
receptors to noradrenaline.
Effects of α1 Stimulation
The α1 receptors are present in vascular
smooth muscles of cutaneous and
splanchnic circulation, sphincters of
bladder and GI tract and radial muscles of
iris.
 Stimulation of these receptors causes
con- traction or constriction of the
structures in which they are present.
They are equally sensitive to adrenaline
and noradrenaline. The effects are
mediated by formation of intracellular IP3.
Effects of α2 Stimulation
α2 receptors are present in
presynaptic nerve endings, wall
of GI tract, platelets and
adipocytes.
Stimulation of these receptors
often causes relaxation or
inhibition of the structure.
The effects are mediated by
decreased formation of
intracellular cAMP.
Effects of β Receptor
Stimulation
β1 receptors are present in SA
node, AV node and ventricular
muscle.
Stimulation of these receptors
causes excitation of these
structures.
They are more sensitive to
adrenaline than noradrenaline.
The effects are mediated by
increased formation of
β2 receptors are present in blood
vessels of skeletal muscles, bronchial
smooth muscles and wall of GI tract.
Stimulation of these receptors causes
relaxation of these structures.
They are more sensitive to adrenaline
than noradrenaline.
The effects are mediated by change in
the level of intracellular cAMP.
β3 receptors are present in
adipose tissues.
 Stimulation of these receptors
causes lipolysis.
The effect is mediated by
increase in the level of
intracellular cAMP.
Fight­or­Flight Response
Widespread response of
sympathetic activation.
Occurs in critical situations of life
when one has to either fight the
situation or flee from the situation.
Many components of response are
due to direct effects of sympathetic
stimulation, secretion of
catecholamine from adrenal
medulla contributes considerably.
Sympathetic stimulation of CVS increases
blood pressure due to increased cardiac
output and vasoconstriction.
Redistribution of the blood flow occurs to
skeletal muscles and heart from splanchnic
and cutaneous territories so that
performance enhances.
In lungs, increased exchange of blood gases
occurs due to stimulation of the respiratory
rate and dilation of bronchiolar tree.
This increases supply of oxygen to the
tissues.
 Sympathetic stimulation to salivary gland
decreases salivary secretion.
 Secretion of mucus increases proportionately,
permitting lubrication of the mouth despite
increased ventilation and reduced salivation.
 Supply of metabolic substrates increases, which is
an essential component of effective stress reaction.
 The demand for increased supply of substrates like
glucose and fatty acids is met by the actions of
circulating epinephrine on hepatocytes and
adipocytes.
 Glycogenolysis increases plasma glucose
concentration and lipolysis promotes plasma free
fatty acid level.
Sympathetic stimulation to sweat glands
causes secretion of a watery fluid, and
evaporation of body heat.
Cutaneous vasoconstriction with
concurrent sweat gland activation causes
cold, clammy skin of a frightened
individual.
Activation of piloerector muscles of hair
follicles causes hair standing on the skin.
The hair erection helps in preservation of
body temperature or gives a ferocious
appearance to threaten the enemy
Pupillary dilation enhances visual acuity
and perception to make the individual
environmentally maximal alert.
 Stimulation of brainstem reticular
system makes the individual maximally
alert and mentally conscious to take
appropriate decisions in quick
successions.
Activity of bowel and bladder
temporarily ceases due to constriction
of sphincters
PARASYMPATHETIC FUNCTIONS
Parasympathetic system restores
body’s energy reserve.
Favorable conditions in both
external and internal environ­
ments herald parasympathetic
activation.
Except on cardiovascular system,
most parasympathetic effects are
stimu­latory, especially for the
processes that facilitate energy
storage and growth.
They stimulate intestinal motility,
secretion, digestion and
absorption.
They promote repro­ductive
functions
Most of the parasympathetic
fibers are cholinergic.
Ace­tylcholine is the
neurotransmitter in both pre­and
post­ganglionic fibers.
There are two sets of cholinergic
recep­tors on the target cells:
muscarinic and nicotinic
Muscarinic receptors
Cholinergic muscarinic receptors are
present in heart, smooth muscles and
glands.
These receptors are acti­vated by
acetylcholine and muscarine.
Activation of these receptors produce
inhibitory effects on heart, for
example, decreased heart rate, and
excitatory effects on smooth muscle
and glands, for example, increased GI
motility and secretion etc.
Effects are mediated by
decreased cAMP formation in the
cytosol of cardiac cells and direct
opening of K+ channels in nodal
tissues of heart.
In smooth muscles and glandular
tissues, effects are mediated by
intracellular IP3 and Ca++.
Muscarinic receptors are blocked
by atropine.
Nicotinic Receptors
Cholinergic nicotinic receptors are
present in autonomic ganglia (both
sympathetic and
parasympathetic), neuromuscular
junctions and adrenal medulla.
These receptors are activated by
acetylcholine and nicotine.
Activation of these receptors
produces excitatory effects on
target tissue.
 Effects are mediated by direct
binding of acetylcholine to α subunits
of the receptors.
Receptors also contain Na+ and K+
channels.
Nicotinic effects are blocked by
ganglion blockers such as
hexamethonium that prevent action
of acetyl­choline in the ganglia and at
neuromuscular junction by curare
drugs.
Control of autonomic
functions
Visceral organs are innervated by
sympathetic and para­sympathetic
divisions of autonomic nervous system
(ANS).
 Effects of stimulation of sympathetic
and para­sympathetic systems are
usually opposite.
Due to robust regulatory mechanisms,
the process that acti­vates one division
of ANS usually inhibits and moderates
the function of the other.
Therefore, sympathetic and
parasympathetic divisions are also
reciprocal to each other.
 Consequently, under normal
circumstances exces­sive stimulation
or activation of both the systems,
which might have deleterious effects,
is avoided.
Autonomic functions are regulated by
various reflexes and supraspinal
mechanisms.
Reflex regulation
Previously, ANS was regarded as an
efferent system, and the sensory
neurons (afferents) that innervate
autonomic structures were not
considered as part of ANS.
However, afferent fibers also
constitute an important component
of autonomic system and sensory
input from visceral struc­tures is
part of autonomic organization.
The sensory innervation to the
visceral organs inclu­ding blood
vessels and cutaneous structures
forms the afferent limb of autonomic
reflexes.
The information from visceral organs
reach the spinal cord through afferent
fibers and, from there, the second
order of neurons convey information
to the higher centers via ascending
pathways
Sensory information in the afferent
pathways may not always reach higher
center for finer integration and conscious
perception, but definitely reaches different
levels of autonomic neuraxis up to the level
of subcor­tical structures, especially the
thalamus
 Thus, ANS integrates a hierarchy of
reflexes to control organ functions.
According to their level of integra­tion, the
autonomic reflexes are subjected to control
by various part of CNS.
Ganglia in ANS serves as relay stations
for preganglionic and postganglionic
neurons.
Recent evidences suggest that synaptic
activity in the ganglia may influence
final efferent output.
 Inputs arriving from many preganglionic
neurons alter the activity in ganglia,
which in turn alter the visceral activity.
The best example is the regulation of GI
functions by ganglia of GI tract
Chemoreceptors and mechanoreceptors in
the gut generate afferent action potentials
that pass to the spinal cord and then from
there to the celiac and mesenteric ganglia.
The output from these ganglia changes the GI
motility and secretion required during
digestion.
Ganglia serve as integrative centers for auto­
nomic reflexes.
The example for such integrative func­tions of
ganglia is the parasympathetic ganglia in the
wall of GI tract that finally control GI motility
and secretion
The intrinsic plexuses in the wall
of GI tract serve as the centers
for integration of local or short
reflex activities where input from
parasympathetic pregang­lionic
neurons, postganglionic
sympathetic neurons and local
sensory neurons converge and
interact.
The intrinsic plexuses also
mediate the central or long
Spinal Autonomic Reflexes
Many autonomic reflexes are
integrated in the spinal cord.
The examples are micturition,
defecation and sexual reflexes.
These reflexes are coordinated
by centers in the lumbar and
sacral spinal cord.
 Micturition reflex causes emptying of urinary
blad­der, defecation reflex causes emptying of
rectum, and sexual responses in male cause
erection and ejaculation and in female produce
vaginal lubrication
 Sensory input from the wall of the bladder and
bowel inform the degree of distension of these
hollow viscera.
 Coordination between sympathetic and
parasympathetic systems is required for many
of these responses.
 Higher centers usually inhibit spinal cord
reflex centers.
Autonomic control of micturition
and defecation
Following spinal injury, or in
spinal preparation in animals,
micturition first becomes
involuntary and later becomes
abnormal.
Episodes of hyperten­sion and
piloerection in such patients are
other exam­ples.
Supraspinal (brainstem)
The periaqueductal gray in
midbrain coordinates autonomic
responses to painful stimuli and
induces endogenous analgesia
system.
The nucleus parabrachialis in pons
contribute to respi­ratory and
cardiovascular control.
The locus ceruleus influences
micturition reflexes.
The medullary centers are the key areas
for control of many visceral functions.
The nucleus tractus solitarius receives
sensory infor­mation from cardiovascular,
respiratory and gastro­intestinal receptors.
Vagal efferent fibers arise from this area in
the medulla.
The vasomotor center in the ventrolateral
medulla is the key center for sympathetic
output as it directly controls preganglionic
sympathetic neurons in the spi­nal cord.
Major autonomic reflexes integrated in the
brainstem include:
Pupillary light reflex
Accommodation reflex
Reflex salivation
Reflex lacrimation
Deglutition reflex
Vomiting reflex
Reflexes for regulation of heart rate and
blood pres­sure
Reflexes for regulation of respiration.
Hypothalamus and cortex
provide the highest levels of
autonomic control.
The periventricular
hypothalamus, and medial and
lateral hypothalamic areas
control homeostatic func­tions
such as thermoregulation,
appetite behaviors etc.
Stimulation of lateral and
posterior hypothalamus causes
sympathetic activation, and
stimulation of poste­rior
hypothalamus causes
parasympathetic activation.
Hypothalamus controls circadian
rhythms that influence many
autonomic functions.
Role of Hypothalamus and
Cortex
Hypothalamus also contributes to the
regulation of blood pressure and blood
volume.
For its major role in autonomic functions,
hypothala­mus was designated (by Charles
Sherrington) in the past as ‘head ganglion
of the ANS’.
Hypothalamus, due to its close proximity
and reci­procal interaction with limbic
system, is influenced by limbic activities.
Autonomic functions are easily affected by
limbic functions and dysfunctions.
The prefrontal cortex is involved
in the regulation of autonomic
function.
The amygdala coordinates the
autonomic components of
emotional responses.
Cortex, limbic structures,
brainstem and their spinal
connections for control of
autonomic functions are
Autonomic Function Tests
 Autonomic function tests (AFTs) are performed to con- firm
the clinical diagnosis of autonomic dysfunctions and to assess
the degree of sympathetic and parasympathetic involvement
in the process of dysfunction.
 AFTs are classified as:

Tests for cardiovascular autonomic functions

 Heart rate and Blood pressure (BP) response to standing
 Heart rate and BP response to passive tilting
 Assessing baroreceptor sensitivity (BRS)
 Heart rate response to deep breathing
 Valsalva ratio
 BP response to hand grip
 Cold pressure test .
 Norepinephrine spillage technique
 Standing to lying ratio
 Spectral analysis of heart rate variability (HRV)
Tests for sudomotor functions
Sympathetic skin response
Thermoregulatory sweat test
(TST)
Quantitative sudomotor axon
reflex test (QSART)
Vasomotor test
 Laser Doppler Velocimetry for skin blood flow
measurement
 Cold pressor test

Tests for pupillary functions

 Cocaine test
 Adrenaline test

Tests for bladder functions

 Test for sphincter-detrusor dysynergia
 Cystometrogram

Other methods
 Muscle sympathetic nerve activity (MSNA