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Autonomic Nervous System Summary

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                                      Autonomic Nervous System Summary

                                                   Page 1
Companion PHARM PowerPoint Presentations

IVMS-ANS Pharmacology -Intro to the Autonomic Nervous System

IVMS-ANS Pharmacology- Adrenergic Drugs

IVMS- ANS Pharmacology- Cholinergic Agents

IVMS Autonomic and Cardiovascular Pharmacology Course

-------------------------------------------------------------------------------------------------------------------------------

• The Autonomic Nervous System is divided into sympathetic and parasympathetic
divisions
• Basic plan: Nerve impulses propagate from autonomic sensory receptors (and in some cases:
somatic sensory neurons and special sensory neurons – fight-n-flight mechanism) in visceral
organs and blood vessels to integrating centers in CNS. Then, impulses from the autonomic
motor neurons propagate back to the effector tissues regulating smooth (eg., intestinal walls,
blood vessel walls), cardiac, and many glands.
• Autonomic Nervous System operates without conscious control.
• Autonomic Nervous System is controlled by centers in the hypothalamus, limbic system, brain
stem, spinal cord, and to some extent, by the cerebral cortex.
• Examples of autonomic sensory receptors: chemoreceptors, mechanoreceptors, etc.
• Impulses from these receptors are not consciously sensed, except in severe cases like angina
pectoris.
• Autonomic motor neurons work by increasing or decreasing activities of effector tissues.
• Tissues powered by autonomic motor neurons function to some extent even if their nerve
supply is damaged.
• The structure of Autonomic Nervous System is basically two types of neurons connected in
series. The nucleus of the first neuron is located in the spinal cord or brain; and its axons, after
traveling as part of cranial or spinal nerve, are located in the autonomic ganglion. The nucleus of
the second neuron is located in the autonomic ganglion, and its axons are located in effector
tissue.
• The two types of giant neurons communicate only through Ach, but the second neuron
communicates with effector tissue using Ach or norepinephrine (NE).
• The two types of neurons send their impulses through sympathetic and parasympathetic
divisions.
• Impulses from both the divisions oppose each other.
• The hypothalamus is connected to both the systems.

Anatomy of Autonomic Nervous System
• The axon of the first neuron is a small-diameter, myelinated type B fiber that extends to an
autonomic ganglion.
• The axon of the second neuron is a small-diameter, unmyelinated type C fiber that extends to
visceral effector tissue.



                                        Autonomic Nervous System Summary

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The formation of the spinal nerve from the dorsal and ventral roots

The term spinal nerve generally refer to a mixed spinal nerve, which carries motor, sensory, and
autonomic signals between the spinal cord and the body. Humans have 31 left-right pairs of
spinal nerves, each roughly corresponding to a segment of the vertebral column: 8 cervical spinal
nerve pairs (C1-C8), 12 thoracic pairs (T1-T12), 5 lumbar pairs (L1-L5), and 5 sacral pairs (S1-
S5) and 1 coccygeal pair. The spinal nerves are part of the peripheral nervous system (PNS).

http://en.wikipedia.org/wiki/Spinal_nerve




                              Autonomic Nervous System Summary

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Sympathetic Division of the Autonomic Nervous System
• Preganglionic neurons have their cell bodies in lateral horns of the gray matter in the 12
thoracic segments and the first two lumbar segments of the spinal cord.
• Also known as thoracolumbar division.
• There are two types of autonomic ganglia: sympathetic trunk ganglia and prevertebral ganglia.
• Sympathetic trunk ganglia extend from the base of the skull to coccyx.
• Postsympathetic axons from sympathetic trunk ganglia innervate organs above the diaphragm.
• Prevertebral ganglia lie anterior to the vertebral column and innervate organs below the
diaphragm.
• Three major types: celiac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion.
• Once axons of sympathetic preganglionic neurons pass to sympathetic trunk ganglia, they
connect to (sometimes up to 20) postganglionic neurons in three different ways.
• This way, many sympathetic responses affect almost the entire body simultaneously.
• Path of a sympathetic preganglionic neuron: Anterior root of spinal nerve > intervertebral
foramina > white ramus> sympathetic trunk ganglion > postganglionic neurons.
• Adrenal medulla is an organ that is directly hooked up to sympathetic preganglionic neurons.
• Upon stimulation, adrenal medulla releases epinephrine, norepinephrine, and dopamine directly
into blood. These hormones linger in the blood prolonging the effect of sympathetic stimulation.
• All preganglionic neurons are cholinergic.
• All postganglionic neurons that innervate most sweat glands are cholinergic.
• Most postganglionic neurons are adrenergic.

Parasympathetic Division of the Autonomic Nervous System
• Preganglionic neurons have their cell bodies in the nuclei of four cranial nerves in the brain
stem (III, VII, IX, and X) and in lateral gray horns of the second through fourth sacral segments.
• Also known as craniosacral division.
• Axons of preganglionic neurons emerge as part of a cranial nerve or as part of the anterior root
of a spinal nerve.
• There are two types of preganglionic neuron divisions: cranial parasympathetic outflow (vagus
n; CN X makes up 80% of this) and sacral parasympathetic outflow (anterior roots of S2-S4;
pelvic splanchnic nerves).
• The preganglionic and postganglionic axons synapse in terminal ganglia, which are located in
effector tissues.
• Most of these ganglia are actually located in the visceral effector tissue, so parasympathetic
preganglionic neurons have much longer axons.
• Preganglionic neurons synapse with only 4-5 postganglionic neurons, all of which supply a
single visceral effector.
• Parasympathetic responses can be localized to a single effector.
• All preganglionic neurons are cholinergic.
• All postganglionic neurons are cholinergic.




                               Autonomic Nervous System Summary

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Autonomic Nervous System Neurotransmitters and Receptors
• There are two types of autonomic neurons: cholinergic or adrenergic
• Receptors for neurotransmitters are integral plasma proteins that are located in the plasma
membrane of the postsynaptic neuron or effector cell.

Cholinergic Neurons and Receptors
• They release Ach.
• They are all the sympathetic and parasympathetic neurons, sympathetic postganglionic neurons
that innervate most sweat glands, and all parasympathetic postganglionic neurons.
• ACh from synaptic clefts in presynaptic neurons > binds specific cholinergic receptors in
postsynaptic neurons.
• There are two types of cholinergic receptors: nicotinic receptors and muscarinic receptors.
• ACh causes depolarization in tissues with nicotinic receptors.
• ACh causes depolarization or hyperpolarization in tissues with muscarinic receptors.
• ACh is deactivated by acetylcholinesterase (AChE).

Adrenergic Neurons and Receptors
• Adrenergic neurons release norepinephrine (NE), also known as noradrenalin.
• NE in synaptic vesicles > diffusion across synaptic cleft > bind to adrenergic receptors.
• Adrenergic receptors bind both hormones norepinephrine and epinephrine.
• There are two types of receptors: alpha and beta.
• They are further classified as alpha1 (excitation), alpha2 (inhibition), beta1 (excitation), beta2
(inhibition/relaxation ), and beta3 (present on brown fat; activation causes heat produciton).
• NE action is terminated either when it is reabsorbed back into the releasing axon, or by
enzymatic inactivation by catechol-O-methyltransferase (COMT) and /or monoamine oxidase
(MAO).
• NE creates long lasting effects because its reuptake is slower than that of ACh.

Agonists and Antagonists
• Agonists activate receptors, mimicking the effect of a natural neurotransmitter or hormone.
• Antagonists deactivate receptors.

Physiologic effects of the Autonomic Nervous System
• Sympathetic and parasympathetic systems are in opposition to each other; mediated by the
hypothalamus.
• A few structures receive only sympathetic innervation.

Sympathetic Responses
• It dominates during mental or physical stress.
• 4E’s : exercise, excitement, emergency, and embarrassment.
• Activates the fight-or-fight response.
• Effects are longer lasting than parasympathetic system.

Parasympathetic Responses
• It dominates during periods of relaxation.
• Activates the rest-and-digest response.


                                Autonomic Nervous System Summary

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• SLUDD: salivation, lacrimation, urination, digestion, and defecation.
• Also causes 3D: decrease in heart rate, diameter of airways, and diameter of pupils.



          TABLE 2-2 Receptors of the Sympathetic and Parasympathetic Nervous Systems

                                Sympathetic Nervous System             Parasympathetic Nervous System
Site of Action              Receptor Effect on Site                    Receptor Effect on Site
Smooth muscle; skin and     α1       Contract                          MuscarinicRelax
viscera
Smooth and skeletal muscle α1          Contract                        MuscarinicRelax

                          β2           Relax
Smooth muscle of the lung β2           Relax                          MuscarinicContract
Smooth muscle of the      β2           Relax intestinal wall Contract MuscarinicContract intestinal wall;
gastrointestinal tract                 sphincters                               relax sphincter
                          α1
Heart; SA node            β1           Increase heart rate           MuscarinicDecrease heart rate
Heart; ventricles         β1           Increase contractility and    MuscarinicSmall decrease in
                                       conduction velocity                     contractility
Eye; radial muscle          α1         Mydriasis (dilation of pupil) N/A       N/A
Eye; sphincter muscle       N/A        N/A                           MuscarinicMiosis (constriction of
                                                                               pupil)
Eye; ciliary muscle         β2         Relax                         MuscarinicContract (near vision)
Bladder                     β2         Relax wall Contract sphincter MuscarinicContract wall; relax
                                                                               sphincter
                            α1
Uterus                      α1 β2     Contract Relax                   MuscarinicContract
Penis                       α2        Ejaculate                        MuscarinicErection
Sweat glands                MuscarinicSecrete                          N/A       N/A
Pancreas                    α2        Decrease insulin secretion       N/A       N/A

                            β2         Increase insulin secretion N/A            N/A
Liver                       α1, β2     Glycolysis, gluconeogenesis N/A           N/A
Adipose tissue              β1, β3     Lipolysis                   N/A           N/A
N/A, not applicable; SA, sinoatrial.




Control of Autonomic Functions
• Receptor: located at the distal end of a sensory neuron.
• Sensory neuron: conducts impulses from receptors to CNS.
• Integrating center: located in the hypothalamus and brain stem (thus, we are not aware of their


                                  Autonomic Nervous System Summary

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responses), these centers relay signals from sensory neurons to motor neurons. There are no
integration centers for urination and defecation.
• Motor neurons: relay signals from integrating centers to effectors.
• Effector: they are the smooth muscle, cardiac muscle, or glands.

The autonomic neurons are predominantly responsible for the involuntary regulation of the heart,
smooth muscle and glands. This control is essential to maintain homeostasis and life.

Divisions: Neurons are divided into Preganglionic and postganglionic neurons. Is under
involuntary control. Preganglionic fibres are sited in the midbrain and hindbrain, and T1-S4 of
the spinal cord.
1. Sympathetic system: Short pre - and long postganglionic fibres (See schematic above).
2. Parasympathetic system: Long pre - and short postganglionic fibres.
3. Main innervation: Smooth muscle, heart muscle and glands.
4. Autonomic ganglia: are sited in the head, neck, and abdomen.
5. Sympathetic chain: lies on both sides of the thoracic and lumbar vertebra.

General Functions:
1. Functions at a subconscious level, but is strongly influenced by higher integrative levels i.e.
hypothalamus.
2. Integration of cardiac function.
3. Control of GUT movement i.e. smooth (visceral) muscle.
4. Integrates secretion of various glands (i.e. enteric, endocrine)
5. Regulation of visceral organs and blood vessels.

Regulation/control of the Autonomic Nervous System (Autonomic Nervous System):
The control of the sympathetic and parasympathetic divisions is by higher centers sited in the
hypothalamus. Homeostasis is thereby maintained by hypothalamic integration of the Autonomic
Nervous System and Neuroendocrine systems. This is possible by the secretion of releasing
factors and release-inhibiting factors. The cerebral cortex, hypothalamus and limbic systems
work in concert to affect homeostasis.

Parasympathetic System: Brainstem and sacral outflow of spinal cord.

Divisions:
1. Cranial outflow: Visceral structures of the head are supplied by the cranial nerves
(oculomotor, facial, glossopharyngeal and vagus nerves) relaying through the ciliary,
sphenopalatine, submaxillary and otic ganglion.
2. Sacral outflow (pelvic nerve - S2, 3, 4).
3. Length of fibres: Long preganglionic fibres relay on short postganglionic neurons located
adjacent or near the visceral structures.
4. Association with parasympathetic extracranial ganglia (ciliary, pterygopalatine, submandular
and otic ganglia).




                                Autonomic Nervous System Summary

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Mechanism of Action: Stimulation results in -
1. Heart: Bradycardia (slowing of the heart).
2. Lungs (bronchi): Bronchoconstriction.
3. Pupil: Constriction.
4. GIT: Increased peristalsis, sphincters relaxed.
5. Blood vessels: Dilatation of visceral blood vessels.
6. Sweat glands and hair follicles: Regulated by sympathetic system.
7. Responses 1-6 are due to the release of acetylcholine from postganglionic fibres. The results
just the opposite (antagonistic) to the effects of sympathetic stimulation.

Innervation:
1. Cranial nerves, eye, lacrimal gland, submandibular gland, sublingual gland and parotid gland.
Vagus innervates widely (heart, larynx, trachea, bronchi, lung, small bowel, abdominal vessels,
liver, gallbladder, bile ducts, pancreas, kidney and ascending colon.
2. Sacral outflow (S1 - 4). Descending colon, sigmoid and rectum, bladder, sex organs and
external genitalia.

Sympathetic System: - Thoraco-lumbar section of spinal cord.

Divisions:
1. Spinal component (axons). Segments T1 - L3 (thoraco-lumbar outflow).
2. Superior, middle, inferior, cervical ganglia.
3. Sympathetic ganglionated (paravertebral) chain, white and gray rami communicantes.
4. Greater, lesser and small splanchnic nerves.
5. Ganglia: Coeliac, superior mesenteric and inferior mesenteric (termed collateral or
Prevertebral ganglia).
6. Long postganglionic fibres.

Thoracic splanchnic nerves:
1. Chief source of sympathetic nerves for the abdomen.
2. Greater, lesser and lowest are important (visible, once the lung is removed during thoracic
dissection of the cadaver).
3. The nerves contain preganglionic fibres and originate from the 5th to the 12th thoracic
sympathetic ganglia.
4. Twigs are sent to the Celiac ganglia and renal plexus.

Sympathetic chain and ganglia:
1. Are visible on both sides of the thoracic and lumbar vertebra. Union of the two chains occurs
at the ganglion impar sited on the coccyx. Therefore the chains pass through the posterior aspect
of the abdominal cavity into the pelvis.
2. The cervical, thoracic and lumbar sympathetic chains are surgically important, laparoscopic
sympathectomy may be indicated for hyperhidrosis (excessive sweating in the regions of the
Axilla, hands and feet).




                               Autonomic Nervous System Summary

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Rami Communicantes: Arrangement:

Rami communicans (plural rami communicantes) is the term used for a nerve which connects
two other nerves.




Scheme showing structure of a typical spinal nerve. 1. Somatic efferent. 2. Somatic afferent.
3,4,5. Sympathetic efferent. 6,7. Sympathetic afferent.

Gray ramus communicans <Function> After the signals are carried all the way from the spinal
cord to ganglion through ventral ramus, they are synapsed in the ganglions and then post-
ganglionic fibres carry them to the organs that they innervate. But if the response is the whole
body response, as in sympathetic fight or flight, the signals are distributed to other spinal
nerves by way of gray rami which serve as bridges between the spinal nerves.

White ramus communicans The thoracic, and the first and second lumbar nerves each
contribute a branch, white ramus communicans to the adjoining sympathetic ganglion.

They contain myelinated preganglionic sympathetic fibers (GVE and GVA).

Unlike the gray rami, white rami communicantes do not extend below L2 or above T1.


                               Autonomic Nervous System Summary

                                             Page 9
1. Preganglionic neuron fibres pass from the spinal cord via the anterior roots (T1 - T3) and the
white rami comunicantes to the paravertebral sympathetic ganglion chain. Fibres either continue
to the viscera or re-enter the spinal nerve via the grey rami communicantes.




Mechanism of Action: Stimulation results in -
1. Heart: Tachycardia.
2. Lungs: Bronchodilation.
3. Pupil: Dilation.
4. GIT: Inhibited peristalsis, sphincters contracted.
5. Blood vessels: Vasoconstriction.
6. Sweat glands: Increased sweating.
7. Hair follicles: Hair stands on end via m. arrectores pilorum.
8. Responses 1-7 are due to are due to the release of norepinephrine from postganglionic fibres and
the release of epinephrine from the adrenal medulla.

Innervation:
1. Superior cervical ganglion: Fibres pass via the carotid artery plexus and distributed to the eye,
lacrimal, submandibular, sublingual and parotid gland.
2. Middle and inferior cervical ganglion innervate the heart and respiratory tree.
3. T1 - T4: innervate the heart and respiratory tree.
4. T5 - T9: Enter the Coeliac ganglion and then are distributed to the stomach, gut, abdominal
vessels, liver biliary system and pancreas.
5. T10 - T12: via the small splanchnic nerve which relay in the Coeliac and superior mesenteric
ganglia and innervate the adrenal medulla and kidney.
6. L1 - L3 via the inferior mesenteric ganglion innervate the transverse colon downwards,


                                Autonomic Nervous System Summary

                                              Page 10
rectum, bladder and sex organs.
7. The Celiac ganglion, superior and inferior mesenteric ganglion are sited near to the viscera
and are termed collateral ganglia.

Summary: Autonomic System:

Division: Sympathetic (for “flight and fright” reaction) and parasympathetic systems.

Sympathetic System features:
1. Short preganglionic fibres.
2. Ganglionated sympathetic trunk visible in the paravertebral zone. Superior, middle and
inferior ganglia important in the neck (paravertebral ganglia). Occasionally the inferior cervical
ganglion fuses with T1 and forms the Stellate ganglion which overlies the neck of the first rib.
3. Two trunks fuse inferiorly near the coccyx - ganglion impar.
4. Outflow fibres: white rami.
5. Postganglionated fibres: grey rami communicantes.
6. Cranial sympathetic outflow is relayed on the internal carotid artery.
7. Other zones:
a. Cervical sympathetic.
b. Thoracic sympathetic (pulmonary, cardiac plexus: splanchnic nerves - greater, lower, lowest.
c. Lumbar sympathetic - nerves.
d. Pelvic sympathetic - presacral and inferior hypogastric plexus.

Parasympathetic System or Craniosacral System:
1. Cranial parasympathetic outflow: via cranial nerves (3, 6, 9, 10, and 11). Relay in otic, ciliary,
submandibular and sphenopalatine ganglia).
2. Branches of Vagus nerve. Distributed to
a. Cardiac branches.
b. Esophageal branches.
c. Cardiac plexus.
d. Pulmonary plexus.
e. Anterior and posterior gastric nerves.
3. Sacral outflow (S2, 3, 4) - supplies rectum, bladder, uterus, erectile tissue of penis and clitoris,
distal colon.
4, Visceral efferent pathways: consist of three sets of neurons:
a. Upper motor neuron (grey matter of brain).
b. Preganglionic neuron (lower motor neuron i.e. sited in grey matter of brainstem or spinal
cord).
c. Postganglionic neuron (sited in autonomic ganglion).




                                Autonomic Nervous System Summary

                                               Page 11
Autonomic Nervous System Summary

            Page 12
Basic Questions and Answers

1. What are the principal components of the autonomic nervous system (Autonomic Nervous
System)?
Sympathetic and Parasympathetic systems.

2. What is the general function of the Autonomic Nervous System. Contrast this to the function of
the somatic branch of the peripheral nervous system.
Control autonomic processes such as breathing, heart-rate, etc. Somatic branch deals with the (voluntary)
nervous system.

3. How are alpha and beta-receptors related to noradrenaline?
Noradrelin binds to alpha and beta receptors.

4. What are the autonomic effects on the SA node?
Sympathetic: increases heart rate; Parasympathetic: decreases heart-rate.

5. What are the autonomic effects on the ventricular muscle?
Sympathetic: increases heart rate (more powerful contractions); Parasympathetic: decreases heart-rate
(less powerful contractions).

6. Describe the components of the “alarm reaction" and their physiological basis.
Fight-or-flight response

7. What is the physiologic purpose for the tachycardia in the alarm reaction?
This helps to increase blood flow to skeletal muscles, in preparation for fight or flight

8. Which organ produces large amounts of catecholamines in the body?
Epinephrine and norepinephrine are produced by adrenal medulla.

9. What is the effect of increased sympathetic discharge on skin blood flow? On skeletal muscle
blood flow?
Blood is diverted from skin (less priority) to skeletal muscles (high priority) during fight-or-flight
response.

10. A certain category of poisons works by inhibiting acetylcholinesterase – this results in increased
amounts of acetylcholine binding to receptors. Knowing what you know of the effects of
acetylcholine, what signs and symptoms would you expect in a patient who had ingested this sort of
poison?



For further study access:

IVMS Autonomic and Cardiovascular Pharmacology Course




                                   Autonomic Nervous System Summary

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IVMS Autonomic Nervous System Summary

  • 1. Autonomic Nervous System Summary Related Wikipedia link Autonomic ganglion . Autonomic nervous system Celiac ganglia Ciliary ganglion Inferior mesenteric ganglion Inferior mesenteric plexus List of images in Gray's Anatomy: IX. Neurology Otic ganglion Parasympathetic ganglion Parasympathetic nervous system Preganglionic fibers Prevertebral ganglia Pterygopalatine ganglion Satellite glial cell Splanchnic nerves Submandibular ganglion Superior cervical ganglion Superior mesenteric ganglion Superior mesenteric plexus Sympathetic ganglion Sympathetic trunk Thoracic splanchnic nerves Vertebral subluxation Viscus Autonomic Nervous System Summary Page 1
  • 2. Companion PHARM PowerPoint Presentations IVMS-ANS Pharmacology -Intro to the Autonomic Nervous System IVMS-ANS Pharmacology- Adrenergic Drugs IVMS- ANS Pharmacology- Cholinergic Agents IVMS Autonomic and Cardiovascular Pharmacology Course ------------------------------------------------------------------------------------------------------------------------------- • The Autonomic Nervous System is divided into sympathetic and parasympathetic divisions • Basic plan: Nerve impulses propagate from autonomic sensory receptors (and in some cases: somatic sensory neurons and special sensory neurons – fight-n-flight mechanism) in visceral organs and blood vessels to integrating centers in CNS. Then, impulses from the autonomic motor neurons propagate back to the effector tissues regulating smooth (eg., intestinal walls, blood vessel walls), cardiac, and many glands. • Autonomic Nervous System operates without conscious control. • Autonomic Nervous System is controlled by centers in the hypothalamus, limbic system, brain stem, spinal cord, and to some extent, by the cerebral cortex. • Examples of autonomic sensory receptors: chemoreceptors, mechanoreceptors, etc. • Impulses from these receptors are not consciously sensed, except in severe cases like angina pectoris. • Autonomic motor neurons work by increasing or decreasing activities of effector tissues. • Tissues powered by autonomic motor neurons function to some extent even if their nerve supply is damaged. • The structure of Autonomic Nervous System is basically two types of neurons connected in series. The nucleus of the first neuron is located in the spinal cord or brain; and its axons, after traveling as part of cranial or spinal nerve, are located in the autonomic ganglion. The nucleus of the second neuron is located in the autonomic ganglion, and its axons are located in effector tissue. • The two types of giant neurons communicate only through Ach, but the second neuron communicates with effector tissue using Ach or norepinephrine (NE). • The two types of neurons send their impulses through sympathetic and parasympathetic divisions. • Impulses from both the divisions oppose each other. • The hypothalamus is connected to both the systems. Anatomy of Autonomic Nervous System • The axon of the first neuron is a small-diameter, myelinated type B fiber that extends to an autonomic ganglion. • The axon of the second neuron is a small-diameter, unmyelinated type C fiber that extends to visceral effector tissue. Autonomic Nervous System Summary Page 2
  • 3. The formation of the spinal nerve from the dorsal and ventral roots The term spinal nerve generally refer to a mixed spinal nerve, which carries motor, sensory, and autonomic signals between the spinal cord and the body. Humans have 31 left-right pairs of spinal nerves, each roughly corresponding to a segment of the vertebral column: 8 cervical spinal nerve pairs (C1-C8), 12 thoracic pairs (T1-T12), 5 lumbar pairs (L1-L5), and 5 sacral pairs (S1- S5) and 1 coccygeal pair. The spinal nerves are part of the peripheral nervous system (PNS). http://en.wikipedia.org/wiki/Spinal_nerve Autonomic Nervous System Summary Page 3
  • 4. Sympathetic Division of the Autonomic Nervous System • Preganglionic neurons have their cell bodies in lateral horns of the gray matter in the 12 thoracic segments and the first two lumbar segments of the spinal cord. • Also known as thoracolumbar division. • There are two types of autonomic ganglia: sympathetic trunk ganglia and prevertebral ganglia. • Sympathetic trunk ganglia extend from the base of the skull to coccyx. • Postsympathetic axons from sympathetic trunk ganglia innervate organs above the diaphragm. • Prevertebral ganglia lie anterior to the vertebral column and innervate organs below the diaphragm. • Three major types: celiac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion. • Once axons of sympathetic preganglionic neurons pass to sympathetic trunk ganglia, they connect to (sometimes up to 20) postganglionic neurons in three different ways. • This way, many sympathetic responses affect almost the entire body simultaneously. • Path of a sympathetic preganglionic neuron: Anterior root of spinal nerve > intervertebral foramina > white ramus> sympathetic trunk ganglion > postganglionic neurons. • Adrenal medulla is an organ that is directly hooked up to sympathetic preganglionic neurons. • Upon stimulation, adrenal medulla releases epinephrine, norepinephrine, and dopamine directly into blood. These hormones linger in the blood prolonging the effect of sympathetic stimulation. • All preganglionic neurons are cholinergic. • All postganglionic neurons that innervate most sweat glands are cholinergic. • Most postganglionic neurons are adrenergic. Parasympathetic Division of the Autonomic Nervous System • Preganglionic neurons have their cell bodies in the nuclei of four cranial nerves in the brain stem (III, VII, IX, and X) and in lateral gray horns of the second through fourth sacral segments. • Also known as craniosacral division. • Axons of preganglionic neurons emerge as part of a cranial nerve or as part of the anterior root of a spinal nerve. • There are two types of preganglionic neuron divisions: cranial parasympathetic outflow (vagus n; CN X makes up 80% of this) and sacral parasympathetic outflow (anterior roots of S2-S4; pelvic splanchnic nerves). • The preganglionic and postganglionic axons synapse in terminal ganglia, which are located in effector tissues. • Most of these ganglia are actually located in the visceral effector tissue, so parasympathetic preganglionic neurons have much longer axons. • Preganglionic neurons synapse with only 4-5 postganglionic neurons, all of which supply a single visceral effector. • Parasympathetic responses can be localized to a single effector. • All preganglionic neurons are cholinergic. • All postganglionic neurons are cholinergic. Autonomic Nervous System Summary Page 4
  • 5. Autonomic Nervous System Neurotransmitters and Receptors • There are two types of autonomic neurons: cholinergic or adrenergic • Receptors for neurotransmitters are integral plasma proteins that are located in the plasma membrane of the postsynaptic neuron or effector cell. Cholinergic Neurons and Receptors • They release Ach. • They are all the sympathetic and parasympathetic neurons, sympathetic postganglionic neurons that innervate most sweat glands, and all parasympathetic postganglionic neurons. • ACh from synaptic clefts in presynaptic neurons > binds specific cholinergic receptors in postsynaptic neurons. • There are two types of cholinergic receptors: nicotinic receptors and muscarinic receptors. • ACh causes depolarization in tissues with nicotinic receptors. • ACh causes depolarization or hyperpolarization in tissues with muscarinic receptors. • ACh is deactivated by acetylcholinesterase (AChE). Adrenergic Neurons and Receptors • Adrenergic neurons release norepinephrine (NE), also known as noradrenalin. • NE in synaptic vesicles > diffusion across synaptic cleft > bind to adrenergic receptors. • Adrenergic receptors bind both hormones norepinephrine and epinephrine. • There are two types of receptors: alpha and beta. • They are further classified as alpha1 (excitation), alpha2 (inhibition), beta1 (excitation), beta2 (inhibition/relaxation ), and beta3 (present on brown fat; activation causes heat produciton). • NE action is terminated either when it is reabsorbed back into the releasing axon, or by enzymatic inactivation by catechol-O-methyltransferase (COMT) and /or monoamine oxidase (MAO). • NE creates long lasting effects because its reuptake is slower than that of ACh. Agonists and Antagonists • Agonists activate receptors, mimicking the effect of a natural neurotransmitter or hormone. • Antagonists deactivate receptors. Physiologic effects of the Autonomic Nervous System • Sympathetic and parasympathetic systems are in opposition to each other; mediated by the hypothalamus. • A few structures receive only sympathetic innervation. Sympathetic Responses • It dominates during mental or physical stress. • 4E’s : exercise, excitement, emergency, and embarrassment. • Activates the fight-or-fight response. • Effects are longer lasting than parasympathetic system. Parasympathetic Responses • It dominates during periods of relaxation. • Activates the rest-and-digest response. Autonomic Nervous System Summary Page 5
  • 6. • SLUDD: salivation, lacrimation, urination, digestion, and defecation. • Also causes 3D: decrease in heart rate, diameter of airways, and diameter of pupils. TABLE 2-2 Receptors of the Sympathetic and Parasympathetic Nervous Systems Sympathetic Nervous System Parasympathetic Nervous System Site of Action Receptor Effect on Site Receptor Effect on Site Smooth muscle; skin and α1 Contract MuscarinicRelax viscera Smooth and skeletal muscle α1 Contract MuscarinicRelax β2 Relax Smooth muscle of the lung β2 Relax MuscarinicContract Smooth muscle of the β2 Relax intestinal wall Contract MuscarinicContract intestinal wall; gastrointestinal tract sphincters relax sphincter α1 Heart; SA node β1 Increase heart rate MuscarinicDecrease heart rate Heart; ventricles β1 Increase contractility and MuscarinicSmall decrease in conduction velocity contractility Eye; radial muscle α1 Mydriasis (dilation of pupil) N/A N/A Eye; sphincter muscle N/A N/A MuscarinicMiosis (constriction of pupil) Eye; ciliary muscle β2 Relax MuscarinicContract (near vision) Bladder β2 Relax wall Contract sphincter MuscarinicContract wall; relax sphincter α1 Uterus α1 β2 Contract Relax MuscarinicContract Penis α2 Ejaculate MuscarinicErection Sweat glands MuscarinicSecrete N/A N/A Pancreas α2 Decrease insulin secretion N/A N/A β2 Increase insulin secretion N/A N/A Liver α1, β2 Glycolysis, gluconeogenesis N/A N/A Adipose tissue β1, β3 Lipolysis N/A N/A N/A, not applicable; SA, sinoatrial. Control of Autonomic Functions • Receptor: located at the distal end of a sensory neuron. • Sensory neuron: conducts impulses from receptors to CNS. • Integrating center: located in the hypothalamus and brain stem (thus, we are not aware of their Autonomic Nervous System Summary Page 6
  • 7. responses), these centers relay signals from sensory neurons to motor neurons. There are no integration centers for urination and defecation. • Motor neurons: relay signals from integrating centers to effectors. • Effector: they are the smooth muscle, cardiac muscle, or glands. The autonomic neurons are predominantly responsible for the involuntary regulation of the heart, smooth muscle and glands. This control is essential to maintain homeostasis and life. Divisions: Neurons are divided into Preganglionic and postganglionic neurons. Is under involuntary control. Preganglionic fibres are sited in the midbrain and hindbrain, and T1-S4 of the spinal cord. 1. Sympathetic system: Short pre - and long postganglionic fibres (See schematic above). 2. Parasympathetic system: Long pre - and short postganglionic fibres. 3. Main innervation: Smooth muscle, heart muscle and glands. 4. Autonomic ganglia: are sited in the head, neck, and abdomen. 5. Sympathetic chain: lies on both sides of the thoracic and lumbar vertebra. General Functions: 1. Functions at a subconscious level, but is strongly influenced by higher integrative levels i.e. hypothalamus. 2. Integration of cardiac function. 3. Control of GUT movement i.e. smooth (visceral) muscle. 4. Integrates secretion of various glands (i.e. enteric, endocrine) 5. Regulation of visceral organs and blood vessels. Regulation/control of the Autonomic Nervous System (Autonomic Nervous System): The control of the sympathetic and parasympathetic divisions is by higher centers sited in the hypothalamus. Homeostasis is thereby maintained by hypothalamic integration of the Autonomic Nervous System and Neuroendocrine systems. This is possible by the secretion of releasing factors and release-inhibiting factors. The cerebral cortex, hypothalamus and limbic systems work in concert to affect homeostasis. Parasympathetic System: Brainstem and sacral outflow of spinal cord. Divisions: 1. Cranial outflow: Visceral structures of the head are supplied by the cranial nerves (oculomotor, facial, glossopharyngeal and vagus nerves) relaying through the ciliary, sphenopalatine, submaxillary and otic ganglion. 2. Sacral outflow (pelvic nerve - S2, 3, 4). 3. Length of fibres: Long preganglionic fibres relay on short postganglionic neurons located adjacent or near the visceral structures. 4. Association with parasympathetic extracranial ganglia (ciliary, pterygopalatine, submandular and otic ganglia). Autonomic Nervous System Summary Page 7
  • 8. Mechanism of Action: Stimulation results in - 1. Heart: Bradycardia (slowing of the heart). 2. Lungs (bronchi): Bronchoconstriction. 3. Pupil: Constriction. 4. GIT: Increased peristalsis, sphincters relaxed. 5. Blood vessels: Dilatation of visceral blood vessels. 6. Sweat glands and hair follicles: Regulated by sympathetic system. 7. Responses 1-6 are due to the release of acetylcholine from postganglionic fibres. The results just the opposite (antagonistic) to the effects of sympathetic stimulation. Innervation: 1. Cranial nerves, eye, lacrimal gland, submandibular gland, sublingual gland and parotid gland. Vagus innervates widely (heart, larynx, trachea, bronchi, lung, small bowel, abdominal vessels, liver, gallbladder, bile ducts, pancreas, kidney and ascending colon. 2. Sacral outflow (S1 - 4). Descending colon, sigmoid and rectum, bladder, sex organs and external genitalia. Sympathetic System: - Thoraco-lumbar section of spinal cord. Divisions: 1. Spinal component (axons). Segments T1 - L3 (thoraco-lumbar outflow). 2. Superior, middle, inferior, cervical ganglia. 3. Sympathetic ganglionated (paravertebral) chain, white and gray rami communicantes. 4. Greater, lesser and small splanchnic nerves. 5. Ganglia: Coeliac, superior mesenteric and inferior mesenteric (termed collateral or Prevertebral ganglia). 6. Long postganglionic fibres. Thoracic splanchnic nerves: 1. Chief source of sympathetic nerves for the abdomen. 2. Greater, lesser and lowest are important (visible, once the lung is removed during thoracic dissection of the cadaver). 3. The nerves contain preganglionic fibres and originate from the 5th to the 12th thoracic sympathetic ganglia. 4. Twigs are sent to the Celiac ganglia and renal plexus. Sympathetic chain and ganglia: 1. Are visible on both sides of the thoracic and lumbar vertebra. Union of the two chains occurs at the ganglion impar sited on the coccyx. Therefore the chains pass through the posterior aspect of the abdominal cavity into the pelvis. 2. The cervical, thoracic and lumbar sympathetic chains are surgically important, laparoscopic sympathectomy may be indicated for hyperhidrosis (excessive sweating in the regions of the Axilla, hands and feet). Autonomic Nervous System Summary Page 8
  • 9. Rami Communicantes: Arrangement: Rami communicans (plural rami communicantes) is the term used for a nerve which connects two other nerves. Scheme showing structure of a typical spinal nerve. 1. Somatic efferent. 2. Somatic afferent. 3,4,5. Sympathetic efferent. 6,7. Sympathetic afferent. Gray ramus communicans <Function> After the signals are carried all the way from the spinal cord to ganglion through ventral ramus, they are synapsed in the ganglions and then post- ganglionic fibres carry them to the organs that they innervate. But if the response is the whole body response, as in sympathetic fight or flight, the signals are distributed to other spinal nerves by way of gray rami which serve as bridges between the spinal nerves. White ramus communicans The thoracic, and the first and second lumbar nerves each contribute a branch, white ramus communicans to the adjoining sympathetic ganglion. They contain myelinated preganglionic sympathetic fibers (GVE and GVA). Unlike the gray rami, white rami communicantes do not extend below L2 or above T1. Autonomic Nervous System Summary Page 9
  • 10. 1. Preganglionic neuron fibres pass from the spinal cord via the anterior roots (T1 - T3) and the white rami comunicantes to the paravertebral sympathetic ganglion chain. Fibres either continue to the viscera or re-enter the spinal nerve via the grey rami communicantes. Mechanism of Action: Stimulation results in - 1. Heart: Tachycardia. 2. Lungs: Bronchodilation. 3. Pupil: Dilation. 4. GIT: Inhibited peristalsis, sphincters contracted. 5. Blood vessels: Vasoconstriction. 6. Sweat glands: Increased sweating. 7. Hair follicles: Hair stands on end via m. arrectores pilorum. 8. Responses 1-7 are due to are due to the release of norepinephrine from postganglionic fibres and the release of epinephrine from the adrenal medulla. Innervation: 1. Superior cervical ganglion: Fibres pass via the carotid artery plexus and distributed to the eye, lacrimal, submandibular, sublingual and parotid gland. 2. Middle and inferior cervical ganglion innervate the heart and respiratory tree. 3. T1 - T4: innervate the heart and respiratory tree. 4. T5 - T9: Enter the Coeliac ganglion and then are distributed to the stomach, gut, abdominal vessels, liver biliary system and pancreas. 5. T10 - T12: via the small splanchnic nerve which relay in the Coeliac and superior mesenteric ganglia and innervate the adrenal medulla and kidney. 6. L1 - L3 via the inferior mesenteric ganglion innervate the transverse colon downwards, Autonomic Nervous System Summary Page 10
  • 11. rectum, bladder and sex organs. 7. The Celiac ganglion, superior and inferior mesenteric ganglion are sited near to the viscera and are termed collateral ganglia. Summary: Autonomic System: Division: Sympathetic (for “flight and fright” reaction) and parasympathetic systems. Sympathetic System features: 1. Short preganglionic fibres. 2. Ganglionated sympathetic trunk visible in the paravertebral zone. Superior, middle and inferior ganglia important in the neck (paravertebral ganglia). Occasionally the inferior cervical ganglion fuses with T1 and forms the Stellate ganglion which overlies the neck of the first rib. 3. Two trunks fuse inferiorly near the coccyx - ganglion impar. 4. Outflow fibres: white rami. 5. Postganglionated fibres: grey rami communicantes. 6. Cranial sympathetic outflow is relayed on the internal carotid artery. 7. Other zones: a. Cervical sympathetic. b. Thoracic sympathetic (pulmonary, cardiac plexus: splanchnic nerves - greater, lower, lowest. c. Lumbar sympathetic - nerves. d. Pelvic sympathetic - presacral and inferior hypogastric plexus. Parasympathetic System or Craniosacral System: 1. Cranial parasympathetic outflow: via cranial nerves (3, 6, 9, 10, and 11). Relay in otic, ciliary, submandibular and sphenopalatine ganglia). 2. Branches of Vagus nerve. Distributed to a. Cardiac branches. b. Esophageal branches. c. Cardiac plexus. d. Pulmonary plexus. e. Anterior and posterior gastric nerves. 3. Sacral outflow (S2, 3, 4) - supplies rectum, bladder, uterus, erectile tissue of penis and clitoris, distal colon. 4, Visceral efferent pathways: consist of three sets of neurons: a. Upper motor neuron (grey matter of brain). b. Preganglionic neuron (lower motor neuron i.e. sited in grey matter of brainstem or spinal cord). c. Postganglionic neuron (sited in autonomic ganglion). Autonomic Nervous System Summary Page 11
  • 12. Autonomic Nervous System Summary Page 12
  • 13. Basic Questions and Answers 1. What are the principal components of the autonomic nervous system (Autonomic Nervous System)? Sympathetic and Parasympathetic systems. 2. What is the general function of the Autonomic Nervous System. Contrast this to the function of the somatic branch of the peripheral nervous system. Control autonomic processes such as breathing, heart-rate, etc. Somatic branch deals with the (voluntary) nervous system. 3. How are alpha and beta-receptors related to noradrenaline? Noradrelin binds to alpha and beta receptors. 4. What are the autonomic effects on the SA node? Sympathetic: increases heart rate; Parasympathetic: decreases heart-rate. 5. What are the autonomic effects on the ventricular muscle? Sympathetic: increases heart rate (more powerful contractions); Parasympathetic: decreases heart-rate (less powerful contractions). 6. Describe the components of the “alarm reaction" and their physiological basis. Fight-or-flight response 7. What is the physiologic purpose for the tachycardia in the alarm reaction? This helps to increase blood flow to skeletal muscles, in preparation for fight or flight 8. Which organ produces large amounts of catecholamines in the body? Epinephrine and norepinephrine are produced by adrenal medulla. 9. What is the effect of increased sympathetic discharge on skin blood flow? On skeletal muscle blood flow? Blood is diverted from skin (less priority) to skeletal muscles (high priority) during fight-or-flight response. 10. A certain category of poisons works by inhibiting acetylcholinesterase – this results in increased amounts of acetylcholine binding to receptors. Knowing what you know of the effects of acetylcholine, what signs and symptoms would you expect in a patient who had ingested this sort of poison? For further study access: IVMS Autonomic and Cardiovascular Pharmacology Course Autonomic Nervous System Summary Page 13