Lecture 5 ANS CSF KL Revision 3

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    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

    pathwayconsists oftwo 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.

    The autonomic nervous systemis subdivided into sympathetic and parasympathetic divisions based on

    location, pathway and desired response in the body.

    Image Courtesy: Pasedena.edu

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    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 specificlevels: 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

    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.

    ACHAcetylcholine is released by:

    All preganglionic fibers

    -

    Both sympathetic and parasympathetic

    All postganglionic parasympathetic fiberswill

    release ACH. This leads to the activation of

    nicotinic ACH receptors on peripheral targets.

    Epinephrine and Norepinephrine (NE) is

    released by:

    The majority postganglionic sympatheticfibers

    acting on glands, smooth muscle and cardiac

    muscle.

    ACH

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    Exception:

    Postganglionic sympatheticfibers will release

    ACH instead of NE in two cases:

    -sweat glands and smooth muscle surrounding

    hair follicles. This leads to activation of

    muscarinic receptors.

    All nerve fibers that release ACH are referred to

    as cholinergic

    The adrenal medullawill 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

    Receptors

    The response of the

    receptor on the post-

    synaptic 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

    receptorsare activated by

    the binding of ACH or a

    water soluble toxin called:

    Muscarine. This is a water-

    soluble 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 parasympatheticjunction (will either increase or decrease the activity of

    effector cells)

    2.

    Post-synaptic sympathetic stimulationof sweat glands: postganglionic sympathetic neurons

    innervating sweat glands will release ACH at the neuro-effector junction. Activation will result in

    increased sweating.

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    Nicotinic receptorsare characterized by their interaction with nicotine. These receptors are located

    post-synaptically in all autonomic gangliaand 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 originateinside 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.

    There are a few possible routesthat preganglionic sympathetic axons can take when they enter the

    sympathetic chain:

    Image courtesy: University of Western Ontario

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    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 pre-

    vertebral ganglion located close to target tissue.

    Pre-vertebral gangliaare 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. Pre-

    synaptic 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 cardiopulmonarysplanchnic 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 theyreceive 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 wellas spinal cord levels S2-4.

    Cranial nerves containing parasympathetic outflow will have long preganglionicneurons 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.

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    CRANIAL NERVE TARGET ORGAN

    CN III CILIARY MUSCLE OF EYE

    CN VII LACRIMAL GLAND

    SUBMANDIBULAR AND SUBLINGUAL GLANDSCN IX PAROTID GLAND

    CN X DIRECT TARGET ORGAN STIMULATION

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    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 catabolicfight or flight and the parasympathetic division is anabolic rest and digest.

    TARGET SYMPATHETIC Division PARASYMPATHETIC Division

    EYES Pupillary dilation Pupillary constriction

    GLANDS (Tear duct and Salivary) Minimal change Increased gland secretion

    LUNGS Bronchodilation Bronchoconstriction

    HEART Increase heart rate and

    contractile force

    Decrease heart rate

    GI SYSTEM Decreases peristalsis Increases peristalsis to promote

    digestion

    LIVER Encourages glycogenolysis inliver, inhibits gall bladder

    Stimulates bile production,stimulates pancreas secretion

    URINARY Inhibits urination 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 threateningconditions. 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).

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    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 craniumthe 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 butinstead 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 materis 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

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    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 materis 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 layerof dura mater exits the skull via the foramen magnum and together with

    the arachnoid, forms a loose sac-like outer-covering known as the spinaldural 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

    terminaleis 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 equineand filum

    terminale (image to the

    left).

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    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.

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    CSF is produced by a capillary network in the ventricles known as the choroid plexusat 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:

    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.

    Central Canal of Spinal cord

    Fourth Ventricle

    Cerebral Aqueduct

    Third Ventricle

    Interventricular Foramina

    Lateral Ventricles

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    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 Non-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

    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 tumorCyst / 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

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    eyesand 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 afracture of themiddle cranial fossa. CSF Rhinorrheais

    leakage of CSF through the nose which results from a fracture of the anterior cranial fossa specifically

    involving the ethmoid.

    Intracranial hemorrhagesare 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

    Disc Shape on

    CT scan

    Arterial Usually follows trauma (ie/ fracture of skull bone) that causes tearin

    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

    Subdural

    Crescent Shape

    on CT scan

    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)

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    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 du

    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 isperformed below the level of the spinal cord to avoid serious

    injury.

    An epidural blockis 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 signalscoming 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.