Lecture 5: ANS; CSF

The Autonomic Nervous System (ANS)

Objectives:
1. Compare the somatic and autonomic nervous systems relative to effectors, efferent pathways
and neurotransmitter released.
2. Explain the anatomical and functional significance of the sympathetic and parasympathetic
ganglia; identify the location of the pre- and post- ganglionic sympathetic and parasympathetic
neurons.
3. Compare and contrast the general functions of the parasympathetic and sympathetic divisions
of the ANS
1. Compare the somatic and autonomic nervous systems relative to effectors, efferent pathways and
neurotransmitter released.
The peripheral nervous system is divided functionally into: somatic (voluntary) and autonomic
(involuntary) systems. The somatic division is responsible for delivering voluntary signals to skeletal
muscle and the autonomic division regulates the activity of glands, cardiac and smooth muscles. Both
systems travel using peripheral nerves to reach their respective destinations. The bodies of somatic
motor neurons are usually located inside the CNS (brain or spinal cord) and their axons travel long
distances to reach the effector organ and deliver a voluntary message. The autonomic nervous system
pathway consists of two motor neurons: one inside the CNS (called preganglionic) and one outside
the CNS (called postganglionic). Pre-ganglionic neurons synapse with postganglionic neurons in
autonomic ganglia located outside the CNS in the periphery.

Image Courtesy: Pasedena.edu

The autonomic nervous system is subdivided into sympathetic and parasympathetic divisions based on
location, pathway and desired response in the body.

In the sympathetic pathway, the bodies of preganglionic neurons originate in the lateral gray horns of
the spinal cord from vertebral levels T1-L2. These neurons have short axons which exit the cord using
the ventral root of spinal nerves and soon after synapse in autonomic ganglia located outside the CNS.
In the parasympathetic pathway, the bodies of preganglionic neurons originate in the brainstem or
sacral division of the spinal cord. These neurons have long axons which exit the CNS at only specific
levels: Cranial nerves III, VII, IX, X and spinal nerves S2-4. They synapse in parasympathetic ganglia
located very near or directly inside target organs.
Neurotransmitters of the ANS

ACH
There are two main neurotransmitters acting on target organs in the autonomic nervous system:
Acetylcholine (ACH) and Epinephrine (EPI). Please note that ACH is also a primary neurotransmitter of
the somatic nervous system, however the effect and targets for ACH are different in the autonomic
system. In the somatic nervous system, ACH causes contraction of skeletal muscles by binding at the
neuromuscular junction. In the autonomic nervous system, ACH binding causes a wide variety of
responses discussed in objective #3 of this chapter.
ACH Acetylcholine is released by:
All preganglionic fibers
- Both sympathetic and parasympathetic
All postganglionic parasympathetic fibers will
release ACH. This leads to the activation of
nicotinic ACH receptors on peripheral targets.

Epinephrine and Norepinephrine (NE) is

released by:
The majority postganglionic sympathetic fibers
acting on glands, smooth muscle and cardiac
muscle.

Exception:
Postganglionic sympathetic fibers will release
ACH instead of NE in two cases:
-sweat glands and smooth muscle surrounding
hair follicles. This leads to activation of
muscarinic receptors.

The adrenal medulla will also release NE and

Epinephrine into the bloodstream when
stimulated by pre-ganglionic sympathetic fibers.

All nerve fibers that release NE/EPI are referred

to as adrenergic

All nerve fibers that release ACH are referred to

as cholinergic

Receptors
The response of the
receptor on the postsynaptic cell depends on the
nature of the receptor, not
the neurotransmitter. There
are two distinct types of
receptors that bind
acetylcholine: Muscarinic
and Nicotinic.
Muscarinic Acetylcholine
receptors are activated by
the binding of ACH or a
water soluble toxin called:
Muscarine. This is a watersoluble toxin derived from
the mushroom: Amanita
muscaria. Muscarine has
the capacity to cause substantial activation of the parasympathetic nervous system, resulting in
convulsions and even death. Muscarinic receptors are involved in a large number of physiological
functions including: decreasing the heart rate and inducing contraction of smooth muscles. Muscarine
receptors can be blocked by atropine and scopolamine.
There are 5 subtypes of muscarinic receptors, based on pharmacologic activity (M1-M5). These
receptors are located in two distinct areas:
1. Post-synaptically at the parasympathetic junction (will either increase or decrease the activity of
effector cells)
2. Post-synaptic sympathetic stimulation of sweat glands: postganglionic sympathetic neurons
innervating sweat glands will release ACH at the neuro-effector junction. Activation will result in
increased sweating.

Nicotinic receptors are characterized by their interaction with nicotine. These receptors are located
post-synaptically in all autonomic ganglia and at the neuromuscular junction. These receptors can be
blocked by the plant toxin curare and some snake venoms. Competitive binding of these toxins will
lead to weakness of skeletal muscles and eventual death due to paralysis of the diaphragm. In
myasthenia gravis, nicotinic receptors are destroyed by antibodies which will result in progressive
muscle weakness and eventual paralysis.
2. Explain the anatomical and functional significance of the sympathetic and parasympathetic ganglia;
identify the location of the pre- and post- ganglionic sympathetic and parasympathetic neurons.
The Sympathetic Division Thoraco-lumbar outflow.
Pre-ganglionic myelinated axons originate inside the lateral grey horns of the spinal cord from segments
T1-L2, hence referred to as a thoraco-lumbar outflow. These axons leave the spinal cord via ventral
roots of spinal nerves and synapse in peripheral ganglia. Anatomically, there are three kinds of
sympathetic ganglia: paravertebral, pre-vertebral and the suprarenal medulla. The paravertebral
ganglia are located beside the vertebral column linked together in a chain sequence; for this reason
they are commonly called the sympathetic trunk. These chains extend along the entire length of the
vertebral column from cervical spine to the coccyx. The cell bodies of post-ganglionic sympathetic
neurons are located inside these peripheral ganglia.
Axons of preganglionic sympathetic neurons enter paravertebral ganglia via small nerve bridges called:
White Rami Communicantes; once inside the ganglion, the preganglionic axon will synapse. Axons from
post-ganglionic sympathetic neurons will exit the paravertebral ganglia to re-join spinal nerves via nerve
bridges known as: Gray Rami Communicantes.

Image courtesy: University of Western Ontario

There are a few possible routes that preganglionic sympathetic axons can take when they enter the
sympathetic chain:

1. Axon will enter the chain and synapse within the sympathetic chain ganglion at the same level
that the nerve emerges off the spinal cord (shown in the picture on previous page).
2. Axon will ascend or descend using the chain to travel to sympathetic chain ganglia which are
responsible for providing sympathetic innervation to the head/neck or genitourinary system.
3. Axon will not synapse in sympathetic chain but instead travel far distances to synapse in prevertebral ganglion located close to target tissue.
Pre-vertebral ganglia are situated anterior to the vertebral column and aorta. They are usually solitary
structures located between the target organ and the vertebral column. These ganglia are named after
the big branches of the abdominal aorta: Celiac, Superior Mesenteric and Inferior Mesenteric. Presynaptic sympathetic fibers that are involved in innervation of abdominal viscera will pass through the
sympathetic chain at several levels and synapse in the three pre-vertebral ganglia mentioned above.
This nerve arrangement is referred to as the Thoracic and Lumbar Splanchnic nerves (plexuses that are
responsible for innervating thoracic and abdominal viscera).
Alternatively, the post-ganglionic sympathetic neurons that innervate the viscera of the thoracic cavity
will exit from the sympathetic chain at several levels and travel together as part of the cardiopulmonary
splanchnic plexus to reach the target organs such as the heart and lungs.
The suprarenal (adrenal) glands are located above the kidneys and act as specialized sympathetic
ganglia because they receive direct innervation from pre-ganglionic sympathetic fibers. In this case,
there are no post-ganglionic sympathetic fibers, instead the medullary cells of the adrenal glands release
neurotransmitter directly into the blood flow, causing widespread systemic sympathetic response.
The Parasympathetic Division Cranial Sacral Outflow
Preganglionic parasympathetic neurons originate in two distinct locations: grey matter of brain stem and
sacral spinal cord. The preganglionic axons exit the brainstem via cranial nerves III, VII, IX and X as well
as spinal cord levels S2-4.
Cranial nerves containing parasympathetic outflow will have long preganglionic neurons that travel to
peripheral ganglia that are located close to or within target organs. The postganglionic fibers will travel
short distances to influence target organs for the parasympathetic system.
Cranial nerves III, VII, and IX provide parasympathetic innervation to the head, while CN X travels long
distances to provide stimulation to the majority of thoracic and abdominal viscera (making up approx.
85% of the parasympathetic outflow). The chart on the following page indicates the target organ that
are associated with the parasympathetic outflow from the cranial nerves. You will learn more about
these pathways when you study cranial nerves in lecture 9.
The preganglionic parasympathetic fibers from S2-4 travel as pelvic splanchnic nerves and synapse in
intrinsic ganglia located in pelvic organs. Overall the parasympathetic system supplies organs and
glands of the head, thorax, abdomen and pelvis, while it does not reach the body walls or limbs.

CRANIAL NERVE
CN III

TARGET ORGAN
CILIARY MUSCLE OF EYE

CN VII

LACRIMAL GLAND
SUBMANDIBULAR AND SUBLINGUAL GLANDS
PAROTID GLAND
DIRECT TARGET ORGAN STIMULATION

CN IX
CN X

3. Compare and contrast the general functions of the parasympathetic and sympathetic divisions of
the ANS.
The autonomic nervous system regulates the activity of glands, cardiac and smooth muscles. The two
divisions of the ANS innervate the same structures and have coordinated effects in order to provide
constant involuntary modulation of organs and tissues. In general, the sympathetic division is catabolic
fight or flight and the parasympathetic division is anabolic rest and digest.
TARGET
EYES
GLANDS (Tear duct and Salivary)
LUNGS
HEART
GI SYSTEM
LIVER
URINARY

SYMPATHETIC Division
Pupillary dilation
Minimal change
Bronchodilation
Increase heart rate and
contractile force
Decreases peristalsis
Encourages glycogenolysis in
liver, inhibits gall bladder
Inhibits urination

PARASYMPATHETIC Division
Pupillary constriction
Increased gland secretion
Bronchoconstriction
Decrease heart rate
Increases peristalsis to promote
digestion
Stimulates bile production,
stimulates pancreas secretion
Stimulates urination/defecation

Clinical Information: The Pupillary reflex

The pupillary light reflex is an important clinical tool used
to evaluate the function of the brain stem in a comatose
patient. It is also one of the brain stem reflexes tested in
the determination of brain death. Pupillary anomalies
could be indicators of critical or life threatening
conditions. Pupillary constriction and dilation may also
depend on integrity of sympathetic (CN V1) and
parasympathetic (CN III) pathways.

Post-Ganglionic Sympathetic fibers from the superior

cervical ganglion innervate blood vessels and eye muscles
by using the nerve pathway of the opthalamic division of
the trigeminal nerve (CN V1). Eye muscles controlled by
CN V include: dilator pupillae and superior tarsal muscle
that elevates the upper eyelid. Interruption of the
sympathetic pathway to the eye will produce pupillary
constriction (miosis) and eyelid droop (ptosis).

Cerebrospinal Fluid (CSF)

Objectives:
1. Identify the meninges and the contents of the spaces around the spinal cord and around the
brain.
2. Describe the formation of cerebrospinal fluid and follow its circulatory pathways: choroid
plexus, ventricles, apertures, central canal, subarachnoid space, arachnoid villi and sinuses.
3. Discuss congenital abnormalities and clinical applications related to CSF.
1. Identify the meninges and the contents of the spaces around the spinal cord and around the brain.
There are several layers of protection around the brain and spinal cord: bone, connective tissue and
fluid. The connective tissue layer is referred to as the meningeal layer. There are three meningeal
layers that wrap, isolate and protect the entire CNS: Dura mater, Arachnoid mater and Pia Mater.
In the cranium the dura mater
consists of two layers: outer
periosteal layer which is fused to
the periosteum of the skull bone
and the internal meningeal layer
which lies adjacent to the
arachnoid below. The inner layer of
dura mater forms dural reflections
(infoldings) that divide the cranial
cavity into compartments and act
as seat belts supporting parts of
the brain: falx cerebri, tentorium
cerebelli. Travelling within the
dural folds there are large cavities known as dural venous sinuses. These sinuses are filled with carbon
dioxide rich blood that drains from the brain into the internal jugular vein. Around the brain and spinal
cord the Dura mater is separated from the Arachnoid mater by a potential space: the subdural space. In
a normal healthy brain this space is not real but instead the pressure of the cerebrospinal fluid (CSF)
usually presses the arachnoid mater against the dura. However, if injury is sustained then blood may fill
this space causing a subdural hematoma. In a dry cadaver the arachnoid will easily fall away from the
dura mater because they are not attached to each other normally. The pressure of the CSF only makes
them appear to be in contact in a living patient.
The middle meningeal layer: the arachnoid mater is a delicate avascular membrane composed of
fibrous and elastic membranes resembling a spider web. The arachnoid mater has small extensions or
protrusions called: Arachnoid granulations (or arachnoid villi). These extensions allow cerebrospinal

fluid (CSF) to exit the sub-arachnoid space and enter the dural venous sinuses. Once the CSF is drained
into the venous sinus, it can be transported out of the brain by the venous system.
The pia mater is the thin, delicate, transparent layer that is tightly adhered to the surface of the brain
and spinal cord. It is difficult to remove the pia without damaging the underlying tissue.
The subarachnoid space is the space between the pia and arachnoid mater and it is normally filled with
cerebrospinal fluid that cushions and nourishes neural tissue in both brain and spinal cord.
The internal meningeal layer of dura mater exits the skull via the foramen magnum and together with
the arachnoid, forms a loose sac-like outer-covering known as the spinal dural sac around the spinal
cord. This loose outer covering is separated from the vertebral column by the epidural (extradural)
space which is filled with adipose tissue and has a rich blood supply. The dural sac is anchored to the
periosteum of the skull at the foremen magnum and to the coccyx.
In the spinal cord, there are extensions of pia mater that anchor the cord inside the dural sac called
denticulate ligaments.
These ligaments leave the
cord in pairs between the
origin of the dorsal and
ventral roots. The filum
terminale is another
extension of pia mater that
functions to anchor the cord
and the dural sac to the
coccyx.
Note: Spinal cord is shorter
than vertebral canal (ending
at L1/2 disc in adults)
Identify: conus medullaris,
cauda equine and filum
terminale (image to the
left).

In this image, you can see the dural sac which

has been opened to reveal the denticulate
ligaments found between the spinal nerve
roots.
The dural sac extends inferior to the end of the
spinal cord termination, surrounding the cauda
equina and filum terminale.

2. Describe the formation of cerebrospinal fluid and follow its circulatory pathways: choroid plexus,
ventricles, apertures, central canal, subarachnoid space, arachnoid villi and sinuses.
Cerebrospinal fluid (CSF) is a clear liquid that is
functionally similar to blood. It carries nutrient,
gases and other important chemicals. However,
normally is does not contain RBC, has very little
WBC and has a low concentration of proteins. It
also has a different ion concentration when
compared to blood. CSF constantly circulates
around the brain and spinal cord via the
subarachnoid space. CSF acts as a shock absorber
and mechanically protects the delicate tissue of the
brain and spinal cord. Essentially the brain and
spinal cord float in CSF inside the cranial and
spinal cavities. CSF also helps to maintain
homeostasis and provides a healthy chemical
environment for precise neuronal signaling. Minor
changes in the ion composition would disturb the electrical status of the neuronal cell membrane and
influence the generation of action potentials. Lastly, CSF plays a role in the exchange of nutrients and
wastes produced inside the CNS.
In addition to the subarachnoid space, CSF circulates inside cavities found deep in brain tissue. These
cavities are known as ventricles. There are four ventricles that are filled with CSF: two lateral ventricles,
the third ventricle and the fourth ventricle.

CSF is produced by a capillary network in the ventricles known as the choroid plexus at a rate of 500ml
per day. The total amount of CSF in one person is normally 130-150 ml.
Flow of CSF through the CNS:

Lateral Ventricles
Interventricular Foramina

Third Ventricle
Cerebral Aqueduct

Fourth Ventricle
Central Canal of Spinal cord

Once it arrives at the fourth ventricle, CSF will drain into the central canal of the spinal cord and also exit
into the subarachnoid space via three apertures: 1 median and 2 lateral. Once CSF has circulated in the
subarachnoid space, it will drain into the venous blood flow via the arachnoid granulations (arachnoid
villi). These are extensions of the arachnoid mater which allow CSF to drain from the subarachnoid
space to the dural venous sinus: Superior Sagittal Sinus. This sinus located within the dural folds of the
falx cerebri.

3. Discuss congenital abnormalities and clinical applications related to CSF.

Hydrocephalus
A condition caused by the excessive
accumulation of CSF in the skull or cranium.
Normal flow and absorption through the
cranium is dependent on proper CSF
pressure in the head. A build-up of CSF often
causes a dangerous increase in intracranial
pressure. The combination of CSF build up
and the subsequent increase in pressure can
stress the brain tissue and produce a
characteristic set of signs and symptoms.
Hydrocephalus is categorized as either
communicating or non-communicating based on the cause of CSF buildup.
Communicating Hydrocephalus
Also called non-obstructive hydrocephalus as
the CSF can flow freely through the ventricular
spaces
Caused by disruption of CSF uptake into
subarachnoid space
CONGENTIAL CAUSES:
Cytomegalovirus, Rubella, Toxoplasmosis,
Hemorrhaging as a result of birth trauma
ACQUIRED CAUSES:
Prior infection, Meningitis,
Subarachnoid Hemorrhage,
Cerebral Aneurysm

Non-Communicating Hydrocephalus
Also called obstructive hydrocephalus as the
flow of CSF has been blocked at some point in the
ventricular pathway.
CONGENITAL CAUSES:
Aqueductal stenosis
Stenosis of aperture
ACQUIRED CAUSES:
Brain tumor
Cyst / Abscesses
Brain trauma

The characteristic symptom seen in infants is enlargement of the head; the open sutures allow the
infants skull to expand to accommodate the excess CSF. In older children and adults, the skull bones
are fused so intracranial pressure increases and compresses brain tissue. Characteristic symptoms of
hydrocephalus in adults include: severe headache, nausea, dizziness, poor coordination, sun setting

eyes and blurred vision. The rapid increase in intracranial

pressure will actually push the eyes downward producing a
sun-setting eye appearance.
If hydrocephalus develops, the CSF must be drained from the
ventricles as soon as possible. The most common procedure is
known as a hydrocephalus shunt. The purpose of this
procedure is to relieve the pressure on the brain and redirect
fluids.
A short term solution is an external ventricular drain (EVD) also
known as a venticulostomy catheter. This procedure places a
catheter in the ventricle and the fluid is drained into a vial by
the bedside. A long term solution for chronic hydrocephalus is
the ventriculoperitoneal shunt: where fluid is drained to the
abdomen and reabsorbed.
Cerebral Trauma
Fractures of the cranial base can cause rupture of the dura mater and leakage of CSF from inside the
cranial cavity to the outside. Some specific examples include: CSF Otorrhea is leakage of CSF from the
external acoustic meatus. Results from a fracture of the middle cranial fossa. CSF Rhinorrhea is
leakage of CSF through the nose which results from a fracture of the anterior cranial fossa specifically
involving the ethmoid.
Intracranial hemorrhages are also a result of cerebral trauma. Blood can escape into the spaces
between the meningeal layers, producing a characteristic appearance on CT and MRI. These
hemorrhages are classified based on their location within the meningeal layers: epidural, subdural and
subarachnoid.
Hemorrhage

Origin

Development:

Epidural

Arterial

Usually follows trauma (ie/ fracture of skull bone) that causes tearing
of meningeal arteries.
Blood accumulates between the layers of dura and the cranial bone
Leads to brief loss of consciousness followed by a lucid interval,
deterioration of brain function leading to coma
Occlusion of the bleeding vessels and removal of the blood is needed
as an emergency procedure

Venous

Often occur with cerebral contusions which cause tearing of the

bridging veins between dura and arachnoid.
Blood slowly seeps into potential space
Bleeding is typically not as extensive as epidural
Symptoms appear slowly over a period of days post injury (headache,
confusion, dizziness, weakness, lethargy)

Disc Shape on
CT scan

Subdural
Crescent Shape
on CT scan

Subarachnoid
Blood seen
pooling in
subarachnoid
space on CT

Arterial

Results from a ruptured arterial aneurysm

Blood flows into subarachnoid space
Characteristic sign is sudden severe thunderclap headache, severe
nausea and vomiting, pain around the orbit, and dizziness
A secondary complication is often non-obstructive hydrocephalus due
to the presence of blood in the subarachnoid space

Spinal tap or Lumbar Puncture This procedure is performed to

obtain the sample of CSF from the subarachnoid space. The
needle is inserted between L3 and L4, traveling through: skin,
ligaments, epidural space, dura mater, subdural space and
arachnoid to reach the CSF. Reasons to perform a spinal tap
include: sampling CSF for infections, measuring the pressure of
CSF checking for bleeding in subarachnoid space. In an adult
the spinal cord ends at L1/2, therefore the procedure is
performed below the level of the spinal cord to avoid serious
injury.

An epidural block is a procedure in which an anesthetic

agent is injected into the epidural space through a needle
that is passing between lumbar vertebrae or through the
sacral canal. An epidural block inhibits the sensory signals
coming via peripheral nerves before they can enter the
central nervous system. Unlike a spinal tap, an epidural
injection can be performed at any level in the spinal
column to achieve segmental anesthesia.

BLUE BOXES: in M&A pp. 508-509 Occlusion of Cerebral Veins and Dural venous Sinuses. Metastasis of
Tumor cells to Dural Sinuses, Fractures of the cranial base, Dural Origin of Headaches. pp 511 Head
injuires and Intracranial Hemorrhage; pp 514 Cisternal Puncture, Hydrocephalus, Leakage of CSF.