THE AUTONOMIC NERVOUS

SYSTEM

CHEGE
 TEACHING / LEARNING OBJECTIVES
A. Physiology of Autonomic Nervous System
The three functional divisions of the ANS:
•Sympathetic (thoracolumbar division),
•parasympathetic (craniosacral division),
•enteric (intrinsic innervation of the digestive tract)
Contrast sympathetic and parasympathetic branches of ANS:
•length of preganglionic and postganglionic neurons
•neurotransmitters
•receptors at the ganglionic and target organ synapse.
•Adrenal medulla
Segments of Vertebrae
 SOMATIC N. S. AUTONOMIC N. S.

Control Voluntary Involuntary

Neurons Single neuron for each Two neurons (Pre and

effector organ post ganglionic neurons)

Effector organs Skeletal muscles Smooth muscle, cardiac

muscle & glands.

Neurotransmitters and Acetylcholine Ach, NE, Epinephrine,

receptors Nicotinic receptors ….
Adrenergic and
cholinergic
Single neuron, discrete Neurons overlap, diffuse
Neuroeffector junctions with well organized branching networks with
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specific receptors at varicosities with widely
6
effector organ (motor distributed receptors on
 Somatic or autonomic nervous
system?
A

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 Divisions of the ANS
• The two main divisions of the ANS are:
 Sympathetic N. S.: which prepares your body for
activity in stressful situations (in fright, fight or
flight).

 Parasympathetic N. S.: whose overall function is

to conserve energy and regulate vegetative
activities like eating and sleeping.

• The third division is the enteric nervous

system located in the gastrointestinal tract
plexus.
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THE AUTONOMIC NERVOUS SYSTEM
• Also known as the visceral or involuntary nervous
system, the ANS functions without conscious,
voluntary control.
• innervates cardiac muscle, smooth muscle, and
various endocrine and exocrine glands

• influences the activity of most tissues and organ

systems in the body.
• Therefore, the ANS makes a significant
contribution to homeostasis.
• Eg. regulation of BP, GIT responses to food,
contraction of the urinary bladder, focusing of the
eyes, thermoregulation.
 THE AUTONOMIC NERVOUS SYSTEM
• this system may play a role in many systemic diseases
(eg, heart failure) and drugs that affect this system may
improve (eg, β2-adrenergic agonists and asthma) or
exacerbate (eg, α1-adrenergic antagonists and
hypertension) various disease symptoms and processes.

• The ANS is composed of 2 anatomically and functionally

distinct divisions
• sympathetic system and parasympathetic system.
• Both systems are tonically active. I.e they provide some
degree of nervous input to a given tissue at all times.
• Therefore, the frequency of discharge of neurons in both
systems can either increase or decrease.
 THE AUTONOMIC NERVOUS SYSTEM
• As a result, tissue activity may be either
enhanced or inhibited.
• This characteristic of the ANS improves its ability
to more precisely regulate a tissue's function.
Without tonic activity, nervous input to a tissue
could only increase.
• Many tissues are innervated by both systems.
• Because the sympathetic system and the
parasympathetic system typically have opposing
effects on a given tissue, increasing the activity of
one system while simultaneously decreasing the
activity of the other results in very rapid and
precise control of a tissue's function.
 THE AUTONOMIC NERVOUS SYSTEM
• Each system is dominant under certain conditions. The
sympathetic system predominates during emergency
“fight-or-flight” reactions and during exercise.
• The overall effect of the sympathetic system under these
conditions is to prepare the body for strenuous physical
activity.
• More specifically, sympathetic nervous activity will
increase the flow of blood that is well-oxygenated and rich
in nutrients to the tissues that need it, in particular, the
working skeletal muscles.
• The parasympathetic system predominates during quiet,
resting conditions.
• The overall effect of the parasympathetic system under
these conditions is to conserve and store energy and to
regulate basic body functions such as digestion and
urination.
 Hypothalamus
• Preoptic and septal areas control ANS
• Key controls in:
– Temperature regulation
– Regulation of food intake
– Regulation of water intake
 The Sympathetic and Parasympathetic
Divisions of the Nervous System

The autonomic nervous system directs all activities of the body that occur without a
person's conscious control, such as breathing and food digestion. It has two parts:
the sympathetic division, which is most active in times of stress, and the
parasympathetic division, which controls maintenance activities and helps conserve
the body's energy.
 The ANS controls most visceral functions of the body such
as arterial pressure, GIT motility and secretions etc.
This system has the capacity to rapidly and intensively
alter visceral functions.

The ANS is activated mainly by centers located in the

spinal cord, brain stem, hypothalamus and portions of the
limbic cortex.

The ANS is mainly controlled by autonomic reflexes i.e.

subconscious sensory signals from a visceral organ enter
the control centers and return subconscious reflex
responses directly back to the visceral organ to control its
activities.

The efferent autonomic signals are transmitted to the

various body organs through two major routes:
sympathetic and parasympathetic systems.
 SYMPATHETIC NERVOUS SYSTEM

•The sympathetic nervous system fibers originate in

the spinal cord between segments T-1 and L-2 and
pass first into the sympathetic chain and then into
the tissues and organs that are stimulated by
sympathetic nerves.

•Each sympathetic pathway from the cord to the

stimulated tissue is composed of two neurons- a
preganglionic and postganglionic neuron.
•This is in contrast to only a single neuron in the
skeletal motor pathway.
 SYMPATHETIC NERVOUS SYSTEM

• Immediately after they leave the spinal nerve, the

preganglionic sympathetic fibers pass through a white
ramus into one of the ganglia of the sympathetic chain.
• The preganglionic sympathetic fibers then enter into the
sympathetic trunk and either synapse at the ganglion on
the same level,
• or travel up or down the sympathetic trunk to arrive at the
correct spinal level for their action.
• Once they synapse in the sympathetic ganglion in
the sympathetic trunk, they exit the trunk as gray rami to
join the spinal nerve and innervate the appropriate
structure.
• The postganglionic sympathetic neuron thus originates
either from sympathetic chain ganglia or peripheral
sympathetic ganglia.

From these two sources postganglionic fibers travel to

their destinations in the various organs.

Some sympathetic postganglionic fibers pass all the way

thr’ the splanchnic nerves into the adrenal medullae.

There they end directly on neuronal cells that secrete

epinephrine and norepinephrine into the bloodstream.
Overall, the ratio of preganglionic fibers to
postganglionic fibers is about 1:20. The long
postganglionic neurons originating in the ganglion
chain then travel outward and terminate on the
effector tissues.

This divergence of the preganglionic neuron results

in coordinated sympathetic stimulation to tissues
throughout the body.

The concurrent stimulation of many organs and

tissues in the body is referred to as a mass
sympathetic discharge.
 SYMPATHETIC N. S.
• A division of the ANS that
mobilizes the body for activity and
managing stressful situations.

• Commonly referred to as the

fight/flight response.

• The pre-ganglionic neurons

originate from Thoracolumbar
segment of the spinal cord leaving
through the ventral motor roots
and white rami. (From T1 through
to L3).
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 Autonomic ganglia of SNS
• The pre-ganglionic neurons synapse with the
paravertebral ganglia (the sympathetic chain) and
some synapse on the adjacent prevertebral
ganglia.

• The prevertebral ganglia include cervical, celiac,

superior mesenteric and inferior mesenteric
ganglia.

• These ganglia are very close to the spinal cord

making the pre-ganglionic neurons very short and
the post-ganglionic neurons long. (unlike in PNS).
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 Neurotransmitters of SNS
• The pre-ganglionic neurons release Acetylcholine.

• The post-ganglionic neurons’ varicosities release both:

• Classic neurotransmitters:
– Nor epinephrine: from small clear vesicles.

• Non classic NT’s:

– Neuropeptide Y: released from large dense core vesicles.
– ATP: released together with the Nor epinephrine.

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 Receptors of SNS
• The post-ganglionic neurons have nicotinic
receptors.

• The effector organs of the SNS have

adrenoceptors (α & β) . There are
muscarinic receptors specifically for sweat
glands.

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 PARASYMPATHETIC NERVOUS SYSTEM
• The preganglionic neurons of the parasympathetic system
arise from several nuclei of the brainstem and from the
sacral region of the spinal cord (segments S2-S4).
• The axons of the preganglionic neurons are quite long
compared to those of the sympathetic system and synapse
with postganglionic neurons within terminal ganglia which
are close to or embedded within the effector tissues.

• The axons of the postganglionic neurons, which are very

short, then provide input to the cells of that effector tissue.
• The preganglionic neurons that arise from the brainstem
exit the CNS through the cranial nerves.
• The occulomotor nerve (III) innervates the eyes;
the facial nerve (VII) innervates the lacrimal gland, the
salivary glands and the mucus membranes of the nasal
 PARASYMPATHETIC NERVOUS SYSTEM
• the glossopharyngeal nerve (IX) innervates the parotid
(salivary) gland;
• and the vagus nerve (X) innervates the viscera of the
thorax and the abdomen (eg, heart, lungs, stomach,
pancreas, small intestine, upper half of the large intestine,
and liver).

• The physiological significance of this nerve in terms of the

influence of the parasympathetic system is clearly
illustrated by its widespread distribution and the fact that
75% of all parasympathetic fibers are in the vagus nerve.
• The preganglionic neurons that arise from the sacral
region of the spinal cord exit the CNS and join together to
form the pelvic nerves. These nerves innervate the viscera
of the pelvic cavity (eg, descending colon, rectum, bladder,
lower portions of ureter, external genitalia).
 PARASYMPATHETIC N. S.
• A division of the ANS that
regulates restorative, energy
conserving, vegetative
functions.

• The pre-ganglionic neurons

have a craniosacral origin from
the nuclei of the 3rd, 7th, 9th and
10th cranial nerves for he cranial
part and

• The sacral part originates from

S2,3,4 roots of the pelvic
plexus.

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 Autonomic ganglia of PNS
• They are located in or very close to the
effector organs.

• This makes the pre-ganglionic neuron very

long and the post ganglionic neuron short.

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 Neurotransmitters of PNS
• The pre-ganglionic neurons release Acetylcholine.

• The post-ganglionic neurons’ varicosities release both:

• Classic neurotransmitters:
– Acetylcholine from small clear vesicles. Ach binds to
muscarinic receptors and effect the physiological function.

• Non classic NT’s:

– VIP: released from large dense core vesicles upon intense
or high frequency stimulation to augment the action of Ach.
– NO: synthesized on demand by NO synthase in the
varicosities.
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 Receptors of PNS
• The post-ganglionic neurons have nicotinic
receptors.

• The effector organs of the PNS all have

muscarinic receptors.

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Subdivision Nerves Location Chemical General
Employed of Messenger Function
Ganglia

Sympathetic Thoracolumbar Alongside Norepinephri Fight or flight

(T1 to L2-L3) vertebral ne
column

Parasympathetic Craniosacral On or near Acetylcholine Conservation

an effector of body
organ energy
 Neurotransmitters of the ANS
• The 2 most common neurotransmitters released by neurons of the
ANS are acetylcholine and norepinephrine.

• Neurotransmitters are synthesized in the axon varicosities and stored

in vesicles for subsequent release.

• Cholinergic neurons that use acetylcholine as a neurotransmitter

include:

• all preganglionic neurons (sympathetic & parasympathetic)

• all parasympathetic postganglionic neurons

• the sympathetic postganglionic neurons that supply the sweat glands

• Adrenergic neurons that use adrenaline include all postganglionic

sympathetic neurons (except those that go to the sweat glands,
piloerector muscle and a few blood vessels).
 SYNTHESIS OF ACETYLCHOLINE
Neurotransmitters are synthesized in the axon
varicosities and stored in vesicles for subsequent
release.

Acetylcholine is synthesized in certain neurons by

the enzyme choline acetyltransferase from the
compounds choline and acetyl-CoA. Cholinergic
neurons are capable of producing ACh.

Acetylcholinesterase is an enzyme that catalyzes the

breakdown of acetylcholine into choline and acetate.
It is bound with collagen and glycosaminoglycans in
the local connective tissue.
 Receptors for Autonomic Neurotransmitters
1. Nicotinic receptors are found on the cell bodies of all
postganglionic neurons, both sympathetic and
parasympathetic, in the ganglia of the ANS.

They bind acetylcholine and other nicotine-like agents on

autonomic ganglia, adrenal medulla, and the motor end-
plate of skeletal muscle.

• Acetylcholine released from the preganglionic neurons

binds to these nicotinic receptors and causes a rapid
increase in the cellular permeability to Na+ and Ca++ ions.

• The resulting influx of these 2 cations causes

depolarization and excitation of the postganglionic
neurons of the ANS pathways.
 Receptors for Autonomic Neurotransmitters

2. Muscarinic receptors are found on the cell membranes of the effector

tissues and are linked to G proteins and second messenger systems
which carry out the intracellular effects.

• Acetylcholine released from all parasympathetic postganglionic

neurons and some sympathetic postganglionic neurons traveling to
sweat glands binds to these receptors.

• Muscarinic receptors may be either inhibitory or excitatory, depending

on the tissue upon which they are found.

• Eg muscarinic receptor stimulation in the myocardium is inhibitory and

decreases heart rate

• while stimulation of these receptors in the lungs is excitatory, causing

contraction of airway smooth muscle and bronchoconstriction.
 Parasympathetic postganglionic
receptors
• M1 to M5
• M1 AChRs are common in secretory glands
• M2 AChRs are found in cardiac tissue
• M3 AChRs are found in smooth muscles and in
secretion glands
• Act via cAMP, IP3, DAG and Ca.
• Cause endothelial cells to produce EDRF
Endothelium-derived relaxing factor (NO)
 Receptors for Autonomic
Neurotransmitters
There are 2 classes of adrenergic receptors for norepinephrine and
epinephrine, alpha (α) and beta (β).

• there are at least 2 subtypes of receptors in each class: α1, α2, β1 and
β2 and β3.

• All of these receptors are linked to G proteins and second messenger

systems which carry out the intracellular effects.

• Alpha receptors are the more abundant of the adrenergic receptors.

The α1 receptors are more widely distributed on the effector tissues.

• α1 receptor stimulation leads to an increase in intracellular calcium. As

a result, these receptors tend to be excitatory.

• stimulation of α1 receptors causes contraction of vascular smooth

muscle resulting in vasoconstriction and increased glandular
secretion by way of exocytosis.
 Receptors for Autonomic
Neurotransmitters
• All adrenergic receptors and muscarinic receptors are coupled to G
proteins which are also embedded within the plasma membrane.

• Receptor stimulation causes activation of the G protein and the

formation of a the second messenger.

• The function of the intracellular second messenger molecules is to

elicit tissue-specific biochemical events within the cell which alter the
cell's activity.

• In this way, a given neurotransmitter may stimulate the same type of

receptor on 2 different types of tissue and cause 2 different responses

• This is due to the presence of different biochemical pathways within

each tissue.

• Sympathetic stimulation of β3 receptors in adipose tissue causes

lipolysis
 Termination of Neurotransmitter Activity
• For any substance to serve effectively as a neurotransmitter, it must be rapidly
inactivated or removed from the synapse or, in this case, the neuroeffector
junction.

• This is necessary in order to allow new signals to get through and influence
effector tissue function.

• The primary mechanism used by cholinergic synapses is enzymatic

degradation.

• Acetylcholinesterase hydrolyzes acetylcholine to its component choline and

acetate. It is one of the fastest acting enzymes in the body and acetylcholine
removal occurs in less than 1 msec.

• The most important mechanism for the removal of norepinephrine from the
neuroeffector junction is the reuptake of this neurotransmitter into the
sympathetic nerve that released it (50-80%) followed by diffusion away from
nerve endings into surrounding body fluids and into blood.

• Norepinephrine may then be metabolized intraneuronally by monoamine

oxidase (MAO).

• The circulating catecholamines, epinephrine and norepinephrine, are

THE ADRENAL MEDULLA
 SYNTHESIS OF NOREPINEPHRINE AND
EPINEPHRINE
• The cells of the adrenal medulla are considered modified
sympathetic postganglionic neurons. Instead of a
neurotransmitter, these cells release hormones into the
blood.
• Approximately 20% of the hormonal output of the adrenal
medulla is norepinephrine. The remaining 80% is
epinephrine.

• Unlike true postganglionic neurons in the sympathetic

system, the adrenal medulla contains an enzyme that
methylates norepinephrine to form epinephrine.
• The synthesis of epinephrine is enhanced under
conditions of stress. These 2 hormones released by the
adrenal medulla are collectively referred to as the
 SYNTHESIS OF NOREPINEPHRINE AND
EPINEPHRINE

Norepinephrine (NE) is synthesized inside the nerve axon,

stored within vesicles, then released by the nerve when an
action potential travels down the nerve. Below are the details
for release and synthesis of NE:
1. The AA tyrosine is transported into the sympathetic nerve
axon.
2. Tyrosine is converted to DOPA by tyrosine hydroxylase
(rate-limiting step for NE synthesis). The slowest step of a metabolic pathway or enzymic
reaction; the one that determines the rate of appearance of the ultimate product.

3. DOPA is converted to dopamine by DOPA decarboxylase.

4. Dopamine is transported into vesicles then converted to
NE by dopamine β-hydroxylase (DBH).
 SYNTHESIS OF NOREPINEPHRINE
• An action potential traveling down the axon depolarizes
the membrane and causes calcium to enter the axon.
• Increased intracellular calcium causes the vesicles to
migrate to the axonal membrane and fuse with the
membrane,
• which permits the NE to diffuse out of the vesicle into the
extracellular (junctional) space.
• Depending on the nerve other secondary
neurotransmitters (e.g., ATP), is released along with the
NE.
• The NE binds to the postjunctional receptor and stimulates
the effector organ response.
 EPINEPHRINE SYNTHESIS AND RELEASE

•Epinephrine is synthesized from norepinephrine within the

adrenal medulla.
•Preganglionic fibers of the sympathetic nervous system
synapse within the adrenals. Activation of these
preganglionic fibers releases acetylcholine, which binds to
postjunctional nicotinic receptors in the tissue.

•This leads to stimulation of NE synthesis within

adenomedullary cells, but unlike sympathetic neurons, there
is an additional enzyme (phenylethanolamine-N-
methyltransferase) that adds a methyl group to the NE
molecule to form epinephrine.
•The epinephrine is released into the blood perfusing the
glands and carried throughout the body.