University of Jordan

Faculty of Medicine
Department of Physiology & Biochemistry
st
Medical 1 year students, 2020/2021.
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Textbook of Medical Physiology, Guyton, 14th Ed: 763-773, 13th ed:
773-784, 12th ed: 729-738 and 11th ed. P748-760.

AUTONOMIC NERVOUS SYSTEM (ANS):

This nervous division is anatomically distinct from the motor
somatic nervous system, which innervates skeletal muscle. This group of
efferent paths originates from the central nervous system and innervates
heart, smooth muscle, glandular tissue and enteric nervous system. ANS
has two subdivisions, sympathetic and parasympathetic, which together
perform the following functions on effector tissues they innervate.

1. Regulation of the activity of visceral organ systems:

examples of functions under ANS control include:
- heart rate
- arterial blood pressure
- digestion, intestinal motility, secretions (these functions are
controlled in conjunction with hormones.
- emptying of urinary bladder
- secretory activity of respiratory tract and airways resistance
(by regulation of diameter of bronchioles).
By regulation of these functions, ANS plays an important role in
maintaining constancy of internal environment (homeostasis).

2. Rapid responses to specific environmental stimuli,

these include:
- Light: constriction of the pupil to bright light (miosis), and
dilation of pupil to low light (mydriases).
- Temperature: cutaneous vasodilation and sweating in a
warm environment, and vasoconstriction in cold.
- Stress: The ANS (mainly the sympathetic and the adrenal
medulla) mediates the immediate response (fight or flight
response) to threatening stimuli. This involves a series of
well coordinated responses to meet the metabolic demands
for severe physical exertion. The features of this response
include:

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  increase heart rate and force
of contraction.
 Widely dilated pupils.
 Pallor (pale of fear) as blood is
directed to the skeletal muscle.
 Goose pimple.
 Cold sweat.
 Dry mouth.

Characteristics of autonomic responses:

1. Speed of onset: ANS can produce dramatic changes in the

level of activity of organs they innervate within seconds.
Changes in heart rate, sweating, goose pimples, and rise or
fall in blood pressure can take place within few seconds (3-5
sec).

2. Automatic nature: regulation of visceral functions occurs

without conscious control. Some functions are brought
under voluntary control such as urination and defecation
through the participation of voluntary muscles. The impulses
in ANS to target organs are set up reflexively in response to
specific type of sensory information. The reflex responses
are sensitive to emotional states of the body. Stress,
excitements, euphoria, fear, anxiety or anger can influence
reflexes and induce a variety of symptoms, such as sweating,
palpitation, or digestive disturbances.

3. Tonic activity: The ANS fires continuous impulses to target

organs at very low rate. The basal rate of firing is called
“sympathetic tone” and “parasympathetic tone”. These tones
establish basal rate of contractile activity in smooth muscle
cells, and secretory activity of glandular tissues. The activity
of these effector cells can be changed as a result of an
increase or a decrease in the activity of any divisions of the
ANS.

Physiological anatomy:

Two neurons carry impulses of the ANS from the CNS to the
effector organs. The first is known as preganglionic neuron, the cell

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body is located in the CNS (in appropriate nucleus in the brain or in the
lateral gray of the spinal cord). The fibers of preganglionic are small and
myelinated, and usually end within a ganglion where they synapse with
the second neuron called postsynaptic neuron. The second neuron
(postsynaptic) carries impulses to target organ.

DIVISIONS OF ANS:

There are two divisions of the ANS sympathetic and

parasympathetic autonomic nervous systems.

Sympathetic nervous system:

The cell bodies of preganglionic neurons lie in lateral gray of

spinal cord at segmental levels of T1 through L3. Axons leaves spinal
cord via ventral roots, then leave ventral root via white rami
communicans to enter a vertebral ganglion of the sympathetic chain at the
same segmental level. The preganglionic axon then can:
* Synapse with postganglionic cells at the same segmental level.

* Turn cranial or caudal and synapse with sympathetic

postganglionic neuron at higher or lower segmental level.
Synapse may occur at more than one postganglionic neuron.

After synapse with neurons at paravertebral ganglia, axons of second

neurons leave ganglia via gray rami communicans to return to the
corresponding spinal nerve.

* Some preganglionic fibers that enter ganglia pass without any

synapse at the paravertebral ganglia and continue to some ganglia located
in the abdomen known as prevertebral ganglia, where they have the
synapse with the second neuron. There are three unpaired prevertebral
ganglia: celiac, superior mesenteric and inferior mesenteric ganglia.

* Some preganglionic fibers pass without synapse in paravertebral

ganglia and celiac ganglion. These fibers continue to adrenal gland where
they synapse onto chromaffin cells. These cells liberate epinephrine into
blood stream.

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 Synaptic organization of sympathetic ganglia:

Individual postsynaptic neuron in vertebral ganglia can receive

signals from many preganglionic fibers (convergence) and one
preganglionic neuron can relay impulse to many postganglionic neurons
at different segmental levels (divergence). This organization of the
sympathetic system induces widespread effects on target cells innervated
by sympathetic postganglionic fibers.

Parasympathetic nervous system:

The preganglionic fibers arise in appropriate cranial nuclei and in

segments S3 and S4 (sometimes S2, S5 also). These fibers leave the CNS
in the III, VII, IX, and X (vagus) nerves for fibers of cranial origin and in
pelvic nerve for fibers of sacral origin. The preganglionic fibers are long
and go all the way to the effector organ where they synapse with the
second postganglionic neuron located within the tissue of the effector
organ or to a ganglion located very close to the effector organ. The axons
of postsynaptic neurons are short.

Synaptic organization of parasympathetic nervous system:

In parasympathetic there is no or little branching of preganglionic

fibers (divergence). The ratio of pre to post ganglionic neurons is 1:1 or
1:2. As a result of this arrangement, the parasympathetic actions tend to
be more discrete and confined to the innervated organ.

Organization of the autonomic neuroeffector junction:

The terminals of autonomic nerve fibers are unlike terminals of the

somatic motor fibers (skeletal neuromuscular junction). The autonomic
terminals are highly branched forming extensive network of fibers beaded
with small swellings or varicosities. These varicosities are sites from
where transmitter is released.

The receptors on effector cells are scattered widely over the

innervated organ. Unlike skeletal muscle, there is no specialized receptive
region at the effector cell. The effect of ANS on these cells can be
stimulatory or inhibitory. This effect depends on transmitter type,
receptor subtype and changes in functional proteins induced in cell by
binding of transmitter to its receptor.

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 Effects of sympathetic stimulation:

Sympathetic system innervates widely distributed tissues. These

include, sweat glands, smooth muscle cells of blood vessels supplying
skeletal muscle, skin, etc, smooth muscle cells of hair follicles. This
innervation is consistent with diffuse projections of the sympathetic
postganglionic fibers that originate in vertebral ganglia and distribute
with the spinal nerves.
In human, the previously mentioned target tissues do not have
any parasympathetic innervation. Thus, the sympathetic which has
excitatory effects on these tissues regulates:
 Blood pressure (blood vessels supplying skeletal
muscle are major players). In addition to that the
effect on heart also contributes in regulation of
blood pressure.
 Body temperature by the sympathetic effects on
cutaneous blood vessels and sweat glands.

In addition to its effect on widely distributed tissues, sympathetic

system is involved in handling stress responses (fight or flight reaction).
Together with adrenal gland, the sympathetic system is designed to
promote the production of energy for muscular work and to shut down
organs which have nonessential functions in reaction to stressful
situations. These effects on the following systems include:
 Cardiovascular system: effects on vessels will
result in redistribution of blood by enhancing
blood flow to skeletal muscle and reducing blood
flow to skin and mesentery.
Effects on heart: increasing cardiac
output (volume of blood pumped per
minute).
 Respiratory system: causes relaxation of
bronchial muscle which result in
bronchodilation.
 Digestive system: inhibition of motility
and secretion.
 Metabolic effects:
 Mobilization of glucose.
 Increased lipolysis.
 Increased metabolic rate.

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 Effects of parasympathetic stimulation:

Overall, the parasympathetic, in contrast to sympathetic system is

viewed as regulator of activities involved in replenishment of energy
supply and general maintenance of the organism.
The control provided by parasympathetic system is discrete and
selectively directed to individual organs.

The types of actions produced by parasympathetic stimulation

include:
 Gastrointestinal system: increases motility and
secretory activity.
 Glands: increases secretory activity (but
remember sweat glands are under sympathetic
control).
 Heart: decrease rate of contraction (bradycardia).
 Pupil: control pupil diameter by papillary light
reflex (miosis) (regulates the amount of light
falling on retina).
 Accommodation of the lens for near vision.
 Voiding the urinary bladder (micturition).

MOLECULAR BASIS OF PHYSIOLOGICAL ACTIONS

OF THE ANS:

Transmitters:
At ganglion: preganglionic neurons of both sympathetic and
parasympathetic release acetylcholine (Ach).

At effector organs:
- Post ganglionic terminals of
parasympathetic fibers release
acetylcholine.

- Post ganglionic terminals of sympathetic

fibers release norepinephrine. An
exception for sympathetic nerves to sweat

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 glands, which release acetylcholine
(Ach).

The released Ach by parasympathetic system is inactivated by

breakdown by acetylcholinesterase. Epinephrine is inactivated by
recapture by postganglionic nerve varicosities.

Receptors and signal transduction mechanisms:

Receptors are found at postsynaptic or post junctional membranes
and interact with transmitters released from the nerve terminals.
These receptors function as coding system and they have high
degree of specificity. The nature of response elicited in a particular tissue
to a given transmitter is very precise and depends on the properties of
receptor and the signaling mechanisms employed in that tissue.

Receptors at ganglion:

On post synaptic membrane of sympathetic and parasympathetic

there are nicotinic receptors. These receptors are excited by
acetylcholine. The drug nicotine can also stimulate these receptors.
This receptor is similar but not identical (they have different subunit
structures) to nicotinic receptor of the neuromuscular junction. This
receptor gates ligand gated Na+ channel. Activation of this receptor will
cause depolarization on postsynaptic membrane.

Receptors on effector cells:

- Muscarinic receptors:

These cholinergic receptors lie on effector cells of

parasympathetic neuro-effector junctions. They differ from
nicotinic receptors found on ganglia and neuromuscular junction.
Many muscarinic receptors have been known (M1-M5) at these
junctions. All these receptors are coupled to G protein.

- The inhibitory receptor that is found in the heart

(M2) is coupled via G protein to K+ channels. Activation of
this receptor will slow the rate of depolarization.

- Other inhibitory muscarinic receptors

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 are negatively coupled via Gi protein to adenylyl
cyclase and decrease production of c-AMP.

- The excitatory receptors (M1, M3, M5)

found on smooth muscle and glands are coupled
via Gq protein to phospholipase C. This enzyme
increases production of inositol-1,4,5-trisphosphate
(IP3). IP3 causes release of Ca++ from internal
stores in muscle or glands, causing contraction or
secretion.

These receptors are activated by muscarine and inhibited by

atropine.

The targets of muscarinic receptors’ stimulation are illustrated by

muscarine poisoning. These effects include:
 stimulation of secretory activity: salivation,
tearing, sweating, nasal and bronchial secretion.
 Increase gastrointestinal tract motility
vomiting and diarrhea.
 Contraction of urinary bladder urination.
 Slowing of the heart Bradycardia.

These receptors are blocked by atropine from a plant atropa

belladona which induces reversal effects of muscarinic poisoning.
Effects of atropine include:
 Inhibition of glandular secretions dry
mouth, dry eyes, and dry nasal passages.
 Tachycardia. (increase heart rate).
 Loss of pupillary light reflex.
 Loss of ability to focus the lens for near vision.

- Adrenergic receptors:
These receptors respond to catecholamines (epinephrine (EP) and
norepinephrine (NE)).

Two types of receptors are known alpha () and beta ()
receptors.

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 Alpha receptors:
The alpha receptors are subdivided into 1 and 2 receptors.

The alpha 1 (1) receptor is widely distributed on smooth muscles

with the exception of bronchial muscle. NE and EPI are about equally
effective on these receptors.
Stimulation of this receptor produces excitation. This effect
involves IP3 production and release of Ca++ from intracellular stores.
Some (1 are coupled to Ca++ gated channels).
Alpha2 receptors: are found on sympathetic postganglionic nerve
terminals. These receptors are important for self inhibition of NE release.
Similar receptors are found on nonadrenergic terminals are called
Alpha2 heteroreceptors.
These receptors are negatively coupled to adenylyl cyclase via Gi
protein and decrease c-AMP production.

Beta receptors:

These receptors are subdivided into beta1 (1) and beta 2 (2)
receptors. Both of them are more sensitive to catecholamines than alpha
receptors (catecholamines stimulate these receptors at much lower
concentration than stimulation of alpha receptors).
Beta 1 (1) receptors: found on heart and produces
excitation in the heart.
Beta 2 (2) receptors: found on tracheal and bronchial
smooth muscle, in the gastrointestinal
tract, and on smooth muscles of blood
vessels supplying skeletal muscles
(occurs along with alpha 1 receptors).
The 2 receptors are preferentially
activated by EPI rather than NE.

Both receptors are positively coupled to adenylyl cyclase via Gs

protein, and increase c-AMP. This will result in subsequent activation of
protein kinase and phosphorylation of one or more proteins. The response
elicited depends on the role of phosphorylated proteins.

All subclasses of adrenergic receptors can be blocked by specific

blocking agents (antagonists). 1 blockers are useful as antiarythmic
drugs. 2 selective agonist (produce activation of 2 receptor) will dilate
bronchi. This agonist is useful in asthma.