THE AUTONOMIC NERVOUS SYSTEM

MDSC 1001:ENVIRONMENT & HEALTH

DR. FARID F YOUSSEF
OBJECTIVES

1. Define the autonomic nervous and describe the general functions of the ANS
2. Identify the divisions of the ANS and their functional anatomy
3. Compare and contrast the parasympathetic nervous system and the somatic
nervous system.
4. Compare and contrast the features of the parasympathetic and sympathetic
divisions of the ANS.
5. Explain the term dual innervations and its physiological relevance
6. Identify the neurotransmitters released and the receptors they activate in different
parts of the ANS
OBJECTIVES

7. Describe the effect of parasympathetic and sympathetic activities on

different organ systems.
8. Describe and classify the different receptors within the ANS
9. Identify common pharmacological agents that can block either system
and their effects.
10. Explain what is meant by the ‘fight or flight’ response.
11. Describe the role of the Adrenal medulla in the ANS
12. Compare and contrast noradrenaline and adrenaline.
THE AUTONOMIC NERVOUS SYTEM

 Definition - The collection of nerves, ganglia and plexuses that

innervate viscera, smooth muscle and glands.

 Originally defined as only the motor innervation of these

structures now includes the sensory innervation as well.
THE AUTONOMIC NERVOUS SYSTEM

 Responsible for the control of the visceral organs of the body.

 In collaboration with the higher centres plays a vital role in maintaining body
homeostasis.
◦ E.g. of function includes control of GI motility and secretion, heart rate and blood pressure,
sweating and temperature regulation.
 These functions are not under voluntary control and occur ‘unconsciously’.
 The ANS has the capacity to bring about extremely rapid changes in body function.
This is utilized in criminal investigations by the lie detector or polygraph.
GENERAL
ORGANISATION

 The ANS consists of two

nerve fibres
 a pre-ganglionic neuron
 and a post-ganglionic
neuron. v
 The pre-ganglionic neuron
originates from cells within
the CNS and synapses in
specialised ganglia outside
the CNS from which
originate the post-ganglionic
fibres.
DIVISIONS OF THE ANS

 The ANS is divided into two

divisions:
 The Sympathetic Nervous System
 The Parasympathetic Nervous
System

 Occasionally the Enteric

Nervous System is considered
part of the ANS
 Overview of ANS
Sympathetic
• “Fight or flight”
• Catabolic (expend energy)

Parasympathetic
• Feed & breed”, “rest & digest”
• Homeostasis

• Dual innervation of many organs

• having a brake and an accelerator
provides more control
DUAL INNERVATION

 Antagonism - opposing effects of sympathetic and parasympathetic e.g

heart, bronchial smooth muscle
 Synergism - combined action resulting in increased effect in the same
direction e.g salivary gland
 Cooperation - facilitating a process e.g penis + seminal vesicles, during
micturition
SYMPATHETIC NERVOUS SYSTEM

 Also known as the thoracolumbar outflow.

 Pregangionic fibres originate from segments T1 to L2/3 of the spinal cord.
 Fibres originate from cells found in the intermedio-lateral horn of the spinal
cord.
 Fibres exit the spinal cord in the anterior/ ventral root to synapse in the
autonomic ganglia via the white rami communicantes or white ramus.
 These fibres are all myelinated.
 • Preganglionic cell bodies somatic tissues visceral tissues
SYMPATHETIC
in SYSTEM: PREGANGLIONIC (bodyCELL BODIES
wall, limbs) (organs)
intermediolateral gray
• T1 — L2/L3 intermediolateral
• Somatotopic organization gray columns

T1 –
L2/L3 lateral
horn

Moore’s COA5 2006

SYMPATHETIC NERVOUS SYSTEM

 Grey rami communicantes or the grey ramus

refers to fibres that synpase in the
paravetebral chain and then give rise to
postganglionic fibres that enter the spinal
nerves.
 The spinal nerve contains 8% sympathetic
fibres that innervate the sweat glands,
piloerector muscles and blood vessels of the
spinal distribution.
 Postganglionic fibres are generally
unmyelinated C fibres.
SYMPATHETIC NERVOUS SYSTEM

 The paravetebral chain serves as a distribution system for the nerves

originating in T1-L3.
 Once entering the paravetebral ganglia the nerves can:
 synapse at that level
 pass up and down the paravetebral chain and synapse at another level
 pass through the paravetebral chain to synapse in the prevetebral ganglia(the
coeliac or hypogastric plexus)
 pass to the adrenal medulla
SYMPATHETIC SYSTEM: POSTGANGLIONIC CELL BODIES
1. Paravertebral ganglia
• Located along sides of vertebrae
• United by preganglionics into Sympathetic Trunk
• Preganglionic neurons are thoracolumbar (T1–L2/L3) but Paravertebral
postganglionic neurons are cervical to coccyx ganglia
• Some preganglionics ascend or descend in trunk
sympathetic
trunk (chain)
synapse at
same level
Prevertebral
ganglia
• celiac ganglion
• sup. mesent. g.
• inf. mesent. g.

ascend to descend to
synapse at synapse at aorta
higher level lower level
Moore’s COA5 2006
SYMPATHETIC SYSTEM: POSTGANGLIONIC CELL BODIES
2. Prevertebral (preaortic) ganglia
Paravertebral
• Located anterior to abdominal aorta, in ganglia
plexuses surrounding its major branches
• Preganglionics reach prevertebral ganglia
sympathetic
via abdominopelvic splanchnic nerves trunk (chain)

Prevertebral
ganglia
• celiac ganglion
• sup. mesent. g.
abdominopelvic • inf. mesent. g.
splanchnic
nerve
aorta
Moore’s COA5 2006
PARASYMPATHETIC NERVOUS SYSTEM

 CranioSacral outflow.
 Fibres originate from cranial nerves III,VII, IX and X. 75% of all parasympathetic
fibres are found in CN X, the vagus nerve.
 CNIII send fibres to synapse upon the cillary ganglia and also provide innervationn for the pupillary
sphincter.
 CNVII supplies the lacrimal, nasal and submandibular glands
 CNIX supplies the parotid gland
 CNX most of the thorax and abdomen.

 The sacral roots leave via primarily S2 and 3 to form the nervi erigentes; occasionally
S1 and S4 are involved.
 Cranial outflow
• CN III, VII, IX, X
• Four ganglia in head
• Vagus nerve (CN X) is major
preganglionic parasymp.
supply to thorax & abdomen
• Synapse in ganglia within
wall of the target organs (e.g.,
enteric plexus of GI tract)

Sacral outflow
• S2–S4 via pelvic splanchnics
• Hindgut, pelvic viscera, and
external genitalia

Clinical Relevance
» Surgery for colorectal cancer
puts pelvic splanchnics at risk
» Damage causes bladder &
sexual dysfunction
 Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Location of Preganglionic Cell Bodies

Sympathetic Parasympathetic

Thoracolumbar Craniosacral
T1 – L2/L3 levels Brain: CN III, VII, IX, X
of the spinal cord Spinal cord: S2 – S4
 Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Relative Lengths of Neurons
Sympathetic
ganglion target
CNS

short preganglionic long postganglionic

neuron neuron

Parasympathetic
ganglion target
CNS

long preganglionic short postganglionic

neuron neuron
NEUROTRANSMITTERS IN THE ANS

 There are two principal neurotransmitters in the ANS:

 Acetylcholine(ACH)
 Noradrenaline(NA) or norepinephrine

 Neurons are termed cholinergic and adrenergic based upon which

neurotransmitter they release.
NEUROTRANSMITTERS

 All preganglionic fibres release acetylcholine.

 All postganglionic parasympathetic fibres utilise acetylcholine.
 All postganglionic sympathetic fibres utilise noradrenaline except:
 (eccrine) sweat glands
 piloerector muscles
 a few blood vessels
 Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Neurotransmitters
Sympathetic NE (ACh at sweat glands),
ACh, + + / -, α & ß receptors

• All preganglionics release acetylcholine (ACh) & are excitatory (+)

• Symp. postgangl. — norepinephrine (NE) & are excitatory (+) or inhibitory (-)
• Parasymp. postgangl. — ACh & are excitatory (+) or inhibitory (-)
• Excitation or inhibition is a receptor-dependent & receptor-mediated response
Parasympathetic
ACh, +

Potential for pharmacologic ACh, + / -

muscarinic receptors
modulation of autonomic responses
 Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Target Tissues
Sympathetic Parasympathetic
• Organs of head, neck, • Organs of head, neck,
trunk, & external genitalia trunk, & external genitalia
• Adrenal medulla
• Sweat glands in skin
• Arrector muscles of hair
• ALL vascular smooth muscle

» Sympathetic system is distributed to essentially all

tissues (because of vascular smooth muscle)
» Parasympathetic system never reaches limbs or
body wall (except for external genitalia)
SYNTHESIS AND BREAKDOWN OF ACETYLCHOLINE

1. Ach is synthesised in the nerve terminal of cholinergic neurons.

Acetyl CoA + Choline =Acetylcholine
2. Enzyme responsible for this reaction is choline acetyltransferase.
3. Choline is the rate-limiting factor in this reaction. It is taken up from the
surrounding environment and transported to the nerve terminal for Ach synthesis.
4. Packaged into vesicles with each vesicle containing approximately 10,000
molecules of Ach. This is an ATP dependent process.
SYNTHESIS AND BREAKDOWN OF ACETYLCHOLINE

5. Ach is released when an action potential arrives secondary to calcium influx.

6. Once released it binds to nicotinic and muscurinic receptors.
7. Breakdown is via the enzyme acetylcholinesterase, which is found in very high
concentrations within the synaptic cleft. 90% may be hydrolysed before it reaches
the postsynaptic membrane.
ACETYLCHOLINE

 Acetylcholine (Cholinergic) Receptors

 Muscarinic
 Nicotinic
ACETYLCHOLINE

 Muscarinic receptors
 postganglionic parasympathetic fibers innervating heart, smooth muscle and
exocrine glands
 exception: postganglionic sympathetic fibers innervating sweat glands
 blocked by antimuscarinic agents (e.g., atropine)
ACETYLCHOLINE

 Nicotinic receptors
 classically a biphasic response is observed with stimulation at low doses and
inhibition at high doses
 sympathetic and parasympathetic auto-nomic ganglia and the adrenal
medulla
 effects blocked with ganglionic blockers (e.g., trimethaphan, hexamethonium)
ACETYLCHOLINE

 Nicotinic receptors
 neuromuscular junction of skeletal muscle
 effects blocked with neuromuscular blockers (e.g., curare)
SYNTHESIS AND BREAKDOWN OF NORADRENALINE

1. Precursor molecule is the amino acid tyrosine which is actively taken up by adrenergic
nerves and also by the chromaffin cells of the adrenal medulla.
2. Tyrosine is converted to L-dopa in the neuronal cytoplasm; this is the rate limiting step and
the enzyme is tyrosine hydroxylase.
3. Dopa decarboxylase converts L-dopa to dopamine also in the cytoplasm and dopamine is
actively taken up into the synaptic vesicles.
4. Here dopamine is converted to noradrenaline by the enzyme dopamine-ß-hydroxylase.
5. In the chromaffin cells noradrenaline is methylated by phenyl-ethanolamine-N-methyl
transferase (PNMT).
SYNTHESIS AND BREAKDOWN OF NORADRENALINE

6. Once released NA can be:

 Taken up back into the presynaptic nerve terminal
 Diffuse away from the synaptic cleft
 Be inactivated by the enzymes monamine oxidase found in the mitochondria of nerve terminals
and catechol-O-methyl transferase (COMT)
8. Analysis of urinary metabolites provides an idea of the turnover of noradrenaline.
These include metanephrine, vanilmandelic acid (VMA) and homovanillic acid (HVA).
Useful especially in pheochromocytoma.
NORADRENALINE RECEPTORS

 a1 (alpha 1)
 vascular smooth muscle, genitourinary smooth muscle, liver (contraction)
 intestinal smooth muscle (hyperpolarization and relaxation)
 heart (increased contractile force, arrhythmias)
 a2 (alpha 2)
 pancreatic islets (b cells, decreased insulin secretion)
 platelets (aggregation)
 vascular smooth muscle (contraction)
NORADRENALINE RECEPTORS

 b 1 (beta 1)

 heart (increased force and rate of contraction, AV nodal conduction velocity)

 juxtaglomerular cells (increased renin secretion)
 b2 (beta 2)

 smooth muscle [vascular, bronchial, gastrointestinal, genitourinary] (relaxation)

 skeletal muscle (glycogenolysis; uptake of K+)
 liver (glycogenolysis; gluconeogenesis)
THE ADRENAL MEDULLA
 Consists of chromaffin cells.
◦ These are modified neuronal cells and derived from neural crest cells.
 Stimulated by sympathetic nerve fibres, leads to the release of large quantities of
adrenaline and noradrenaline
◦ 80% adrenaline and 20% noradrenaline.
 Effects are principally the same as direct sympathetic stimulation except they are
longer lasting, x5-10.
 The adrenal medulla also can affect sites that do not have direct sympathetic
stimulation.
 The dual sympathetic supply of the SNS and the adrenal medulla provide the body
with a safety factor as each can substitute for each other during times of disease.
NORADRENALINE VS ADRENALINE

 The effects of adrenaline differ from noradrenaline in the following respects:

1. Adrenaline due to its greater effect upon beta receptors influences the heart to a
larger extent than noradrenaline
2. Adrenaline causes only mild constriction of blood vessels in muscle tissue when
compared to noradrenaline. This is significant due to the number of total blood
vessels in the body and thus noradrenaline can greatly increase peripheral
resistance and increase blood pressure.
3. Adrenaline increases tissue metabolism 5-10 times more than noradrenaline.
FIGHT OR FLIGHT RESPONSE/STRESS RESPONSE

 Large mass discharge of the sympathetic nervous system designed to prepare the
body to perform strenuous activity.
 release of adrenaline from the adrenal medulla
 increase in heart rate/ myocardial contractility/arterial pressure
 blood flow to active muscles and decreased flow to GIT and kidneys, not required for rapid motor
activity.
 increased rate of tissue metabolism
 blood glucose level
 muscle strength
 mental activity
 rate of blood coagulation
 Table 3 : Actions of the Autonomic Nervous System
Autonomic Type of
Effector Organ Action
Division Receptor
sympathetic alpha dilation of the pupil
Eye : pupil
parasympathetic muscarinicconstriction of the pupil
Eye : ciliary sympathetic beta allows far vision
muscle parasympathetic muscarinicallows near vision
Lachrymal (tear) sympathetic beta vasoconstriction
glands parasympathetic muscarinicsecretion of tears
vasoconstriction and secretion of mucous
sympathetic alpha with a low enzyme count
Salivary glands
parasympathetic muscarinic secretion of watery saliva with a high
enzyme count
dilation of coronary arteries, increased heart
rate, increased force of contraction,
sympathetic beta
increased rate of pacemaker conduction
Heart alpha
coronary artery constriction
parasympathetic muscarinic
slows, heart rate, reduces contraction and
conduction, constricts coronary arteries
 sympathetic beta dilation
Bronchii
parasympathetic muscarinic constriction and mucous secretion
sympathetic alpha vasoconstriction
Oesophagus
parasympathetic muscarinic peristalsis, secretion of mucous
sympathetic beta inhibition of peristalsis and secretion
Stomach and
alpha vasoconstriction, spinctre contraction
Intestines
parasympathetic muscarinic peristalsis and secretion
Spleen sympathetic alpha contraction
adrenaline and noradrenaline secreted into
Adrenal medulla sympathetic -
the bloodstream
Liver sympathetic beta break down of glycogen (glyogenolysis)
sympathetic beta relaxation
Gall Bladder
parasympathetic muscarinic contraction
alpha inhibition of insulin secretion
Pancreas sympathetic
beta stimulation of insulin secretion
sympathetic alpha vasoconstriction
Descending
beta inhibition of peristalsis and secretion
colon
parasympathetic muscarinic peristalsis and secretion
 sympathetic alpha constriction of sphincter muscles
Sigmoid colon,
beta inhibition of peristalsis and secretion
rectum and anus
parasympathetic muscarinic peristalsis and secretion
sympathetic alpha contraction of sphincter
Bladder beta relaxation of detrusor muscle
parasympathetic muscarinic contraction of detrusor muscle
sympathetic - ejaculation
Penis
parasympathetic muscarinic erection
Clitoris parasympathetic muscarinic erection
alpha contraction
Uterus sympathetic
beta relaxation
Blood vessels in:
Skin sympathetic alpha constriction
Mucosal linings sympathetic alpha constriction
Muscle sympathetic cholinergic dilation
Kidneys sympathetic alpha constriction
Lungs sympathetic alpha constriction
Intracranial sympathetic alpha slight constriction

sweat glands
except palm of sympathetic muscarinic sweating
hands
sweat glands on
sympathetic alpha sweating
palms of hands
Pilomotor
piloerection (making hair "stand on end")
muscles at root sympathetic alpha
horripilation ("goose pimples")
of body hair
lipolysis (break down of fat to release
Adipose tissue sympathetic beta
energy)
CLINICAL CASES

 AF is a 55-year-old woman who had been experiencing heart

palpitations, a throbbing headache, sweating, pain in the abdomen, nausea
and vomiting. Because these symptoms had failed to subside, she went to
see her primary care physician. A urinalysis revealed the presence of
catecholamines and their metabolites, including vanillylmandelic acid
(VMA). A subsequent CT scan confirmed the presence of a tumor in the
adrenal medulla. Surgery to remove the tumor was scheduled.
CLINICAL CASES

 CD is a 44-year-old woman who had spent much of the day

working in her garden. A blustery wind caused her to
unintentionally inhale the insecticide that she was spraying
throughout the garden. When she began wheezing severely, she
was taken to the emergency room. The attending physician
observed other symptoms including constricted pupils and a
slowed heart rate. CD was treated with the intravenous
administration of atropine sulfate.
CLINICAL CASES

 Raynaud’s Phenomena
 Horner’s syndrome
THE AUTONOMIC NERVOUS SYSTEM
MDSC 1001:ENVIRONMENT & HEALTH
DR. FARID F YOUSSEF