SEMINARPRESENTED BY- Dr NIKHIL SRIVASTAVAMODERATED BY- Dr. DEEPIKA KENKERE

NERVOUS SYSTEM- PHYSIOLOGY

CONTENTS INTRODUCTION CELL MEMBRANE POTENTIAL NERVE PHYSIOLOGY PAIN PATHWAY PARASYMPATHETIC SYSTEM SYMPATHETIC SYSTEM MECHANISM OF CONTROL OF BODY TEMPERATURE NERVE INJURIES BIBLIOGRAPHY

INTRODUCTIONThe nervous system is composed of -1. NEURONS transmit nerve impulses along

nerve fibers to other neurons. Neurons typically have a cell body, axons and

dendrites.2. NERVES are made up of bundles of nerve

fibers.3. NEUROGLIA carry out a variety of

functions to aid and protect components of the nervous system.

Dendrites

Myelin sheath

Schwann cell Nucleus of Schwann cell

Axon

Nodes of Ranvier

Terminal dendrites

Organs of the nervous system can be divided into CENTRAL NERVOUS SYSTEM (CNS) PERIPHERAL NERVOUS SYSTEM (PNS) The nervous system provides sensory, integrative, and

motor functions to the body. Motor functions can be divided into the SOMATIC NERVOUS SYSTEM AUTONOMIC SYSTEM

A. SENSORY RECEPTORS

B. INTEGRATIVE FUNCTIONS

C. EFFECTOR ORGANS

GENERAL OUTLINE OF MEMBRANE PHYSIOLOGY DIFFUSION FACILITATED DIFFUSION ACTIVE TRANSPORT

PASSIVE TRANSPORT

The concentration gradient: causing the ions to diffuse down their concentration gradient

The electrical potential: causing ions to be attracted to the opposite charge to the one they carry

FACILITATED DIFFUSION

ACTIVE TRANSPORT

PRIMARY

SECONDARY

SODIUM & POTASSIUM IONS`The two important ions in a nerve cell are K+ and Na+

Both are cations Na+ ions move more slowly across the membrane than K+ or Cl- ionsThis is because although the Na+ ion is smaller than the K+ ionNa+ has a larger coating of water molecules giving it a bigger diameterThis makes the plasma membrane 25 times more permeable to K+ than Na+

In addition to this K+ ions leak out of K+ ion pores when the nerve cell is at rest

So to maintain the high concentration of K+ inside the cell, it has to be actively pumped inwards a bit when the cell is at rest

The result is that the resting potential of the neurone is almost at the equilibrium for K+ ions

K+ leak out a bit and need pumping in Na+ ions, however, are actively pumped

out and kept out

A COUPLED NA+-K+ PUMP

coupled ion pump

plasma membrane

K+

Na+

K+

Na+

Cytoplasm ECF

© 2008 Paul Billiet ODWS

NERVE PHYSIOLOGY Are capable of generating rapidly changing

electrochemical impulses at their membranes.

Resting membrane potential -90 mV

Na+ (outside)-142mEq/L Na+ (inside)- 14 mEq/L K+ (outside)-4 mEq/L K+ (inside)-140 mEq/L Ratio Na+inside/Na+outside=0.1 K+inside/K+outside=35.0

NERVE IMPULSE An electrochemical event that occurs in

nerve cells following proper stimulation. An all-or-none process which is fast acting

and quick to recover. An event that is described by a voltage curve

that is called an action potential. The nerve impulse can be conducted the

entire length of a nerve cell without diminishment (“domino effect”).

OVERVIEW OF NERVE IMPULSE

RESTING STAGE Sodium/Potassium pump

continuously and actively pumps (3) Na+ out of the cell and (2) K+ into the cell.

Na+ channels are closed so Na+ are not able to move into the cell.

K+ channels are open so K+ can diffuse out of the cell.

This generates a separation of charges so that the inside of the cell is relatively – and the outside is relatively +.

The cell will remain in this state (at rest) until it is stimulated.

DEPOLARIZATION STAGE Permeable to Na+

ions “polarized” state

neutralized Depolarization

occurs Widening of

transmembrane channels

Threshold potential

REPOLARIZATION STAGE Na+ channels close K+ Channels open

more Rapid diffusion of K+

ions to the exterior Voltage gated Na+ &

K+ channels

MECHANISMS OF ACTION OF L.A.

Fig.

MECHANISMS OF ACTION

Inhibiting excitation of nerve endings or blocking conduction in peripheral nerves.

Binding to and inactivating sodium channels.

MECHANISMS OF ACTION

Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve.

when a nerve loses depolarization and capacity to propagate an impulse, the individual loses sensation in the area supplied by the nerve

block nerve fiber conduction by acting on nerve membranes

inhibit sodium ion activity

blocks depolarization--> blocks nerve conduction

PAIN

CLASSIFICATION OF PAIN

PAIN

Somatic(somasthetic)

Visceral (from viscera)e.g. angina pectoris, peptic ulcer, intestinal colic, renal colic, etc.

Superficial (from skin & subcutaneous tissue) e.g. superficial cuts/burns, etc.

Deep (from muscles/bones/fascia/periosteum) e.g. fractures/arthritis/fibrositis, rupture of muscle belly

DEFINITIONThe International Association for the Study of Pain

Pain is "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage“

Monheim : “An unpleasant emotional experience usually initiated by noxious stimulus and transmitted over a specialized neural network to the CNS where it is interpreted as such.”

TYPES OF PAIN

Allodynia Hyperalgesia & hypoalgesia Hyperesthesia & hypoesthesia Hyperpathia Causalgia Neuralgia

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Neurovascular Blood Vessels Throbbing, pulsing or pounding

Neuropathic Sensory nervous system

Shooting, sharp, burning pain

Causalgic Sympathetic nervous system

Burning

Muscular Muscles Deep aching, tight

CHARACTERSTICS TYPE SYSTEM AFFECTED CHARACTER

Sensory Receptors :

Sensory input from various external stimuli is thought to be received by specific peripheral receptors that act as transducers and transmit by nerve action potentials along specific nerve pathways toward the central nervous system.

Termed first–order afferents, these peripheral terminals of afferent nerve fibers differ in the form of energy to which they respond at their respective lowest stimulus intensity, that is, are differentially sensitive.

The impulse interpreted is nociceptive (causing pain) if it exceeds the pain threshold

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TYPES OF RECEPTORS

SENSORY RECEPTORS

GENERAL

SENSES

SPECIAL

SOMATIC VISCERAL

SUPERFICIAL DEEPTouch-pressureThermalPain

Pain Proprioception

PainBaroreceptionChemoreception

VisualAuditionOlfactionGustation

Cutaneous Receptors:

Distinguished morphologically as corpuscular and noncorpuscular.

The pacinian corpuscles, in particular, are highly sensitive mechanoreceptors

Other mechanoreceptors are the Meissner corpuscles, Golgi – Mazzoni corpuscles, Ruffini’s ending and Krause bulb.

Functionally three categories of cutaneous receptors are thought to exist: mechanoreceptors, thermo receptors, and nociceptors.

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A nerve ending that responds to noxious stimuli that can actually or potentially produce tissue damage.

Free nerve endings i.e., they are not enclosed in a capsule. The receptors for fast pain are sensitive to mechanical or thermal stimuli of noxious strength.

The receptors for slow pain are sensitive not only to noxious mechanical and thermal stimuli but also to a wide variety of chemicals associated with inflammation.

NOCICEPTORS

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Since pain receptors respond to a wide variety of stimuli, they are called polymodal.

Types of nociceptors : Aδ Mechanical NociceptorsC Polymodal NociceptorsC fibre mechanical nociceptorsHigh threshold cold nociceptors

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MECHANORECEPTORS

Mechanoreceptors, which respond to tactile non painful stimuli.

Divided into two functional groups (rapidly or slowly adapting) depending on their response during stimuli.

Rapidly adapting mechanoreceptors respond at the onset and offset of the stimuli

Slowly adapting mechanoreceptors respond throughout the stimuli duration.

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C – FIBRE MECHANO HEAT SENSITIVE NOCICEPTORS

These fibres are considered polymodal, as they respond to mechanical, heat, cold and chemical stimuli.

Their monotonic increase in activity evokes a burning pain sensation at the thermal threshold in humans (41–49°C).

Subject to fatigue and sensitization modulation.

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A-FIBRE MECHANO-HEAT-SENSITIVE NOCICEPTORS

Activation of these receptors is interpreted as sharp prickling or aching pain.

Owing to their relatively rapid conduction velocities (5–36 m/s), they are responsible for first pain.

Two subclasses of AMHs exist: types I and II. Type I fibres respond to high magnitude heat, mechanical and

chemical stimuli and are termed polymodal AMHs. They are found in both hairy and glabrous skin.

Type II nociceptors are found exclusively in hairy skin. They are mechanically insensitive and respond to thermal stimulation.

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DEEP TISSUE NOCICEPTORS

Unlike cutaneous pain, deep pain is diffuse and difficult to localize, with no discernable fast (first pain) and slow (second pain) components.

In many cases deep tissue pain is associated with autonomic reflexes (e.g. sweating, hypertension and tachypnoea).

Units that do not respond to mechanical stimuli have been termed silent nociceptors. Silent nociceptors are also present within the viscera.

Silent visceral afferents fail to respond to innocuous or noxious stimuli, but become responsive under inflammatory conditions.

Visceral afferents are mostly polymodal C- and A-fibres.

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Aß - fibres Aδ - fibres C- fibres

Threshold Low Medium High

Axon diameter 6-14μm 1-6μm 0.2-1μm

Myelination Yes Thinly No

Velocity 36-90 5-36 0.2-1

Receptor types Mechanoreceptor Mechano/Nociceptor

Nociceptor

Receptive field Small Small Large

Quality Touch Sharp/first pain Dull/second pain

Summary of receptor types

Gate Control Theory

This theory proposed by Melzack and Wall in 1965 This theory of pain takes into account the relative in put

of neural impulses along large and small fibers, the small nerve fibers reach the dorsal horn of spinal cord and relay impulses to further cells which transmit them to higher levels.

The large nerve fibers have collateral branches, which carry impulses to substantia gelatinosa where they stimulate secondary neurons.

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The substantia gelatinosa cells terminate on the smaller nerve fibers just as the latter are about to synapse, thus reducing activity, the result is, ongoing activity is reduced or stopped –gate is closed.

The theory also proposes that large diameter fiber input has ability to modulate synaptic transmission of small diameter fibers within the dorsal horn.

Large diameter fibers transmit signals that are initiated by pressure, vibration and temperature; small diameter fibers transmit painful sensations.

Activation of large fiber system inhibits small fiber synaptic transmission, which closes the gate to central progression of impulse carried by small fibers.

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SENSORY NEURONS

First Order Second Order Third Order

FIRST ORDER NEURON

Each sensory receptor is attached to a first order primary afferent neuron that carries the impulses to the CNS.

The axons of these first-order neurons are found to have varying thickness.

The larger fibers conduct impulses more rapidly than smaller fibers.

Type A fibers Alpha fibers: size - 13 to 20 µm, velocity - 70 to 120 m/ s. Beta fibers: size – 6 to 13 µm, velocity – 40 to 70 m/s. Gamma fibers: size – 3 to 8 µm, velocity – 15 to 40 m/s. Delta fibers: size – 1 to 5 µm, velocity – 5 to 15 m/s.

Type C fibers Size – 0.5 to 1 µm, velocity – 0.5 to 2 m/s.

SECOND ORDER NEURON The primary afferent neuron carries impulse into the

CNS and synapses with the second-order neuron. This second-order neuron is sometimes called a

transmission neuron since it transfers the impulse on to the higher centers.

The synapse of the primary afferent and the second-order neuron occurs in the dorsal horn of the spinal cord.

THIRD ORDER NEURON

Cell bodies of third order neurons of the nociception-relaying pathway are housed in: the ventral posterior lateral, the ventral posterior inferior, and the intralaminar thalamic nuclei

Third order neuron fibers from the thalamus relay thermal sensory information to the somesthetic cortex.

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FAST PAIN & SLOW PAIN Fast Pain Also known as Sharp pain, pricking pain or acute pain. Easily localized. Not felt in the deep visceral organs. Slow Pain Also known throbbing pain, aching pain or chronic pain.It can occur both in skin and in almost any deep tissue or

organ.

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PAIN PATHWAYS AND MEDICATIONS

Pain Pathways Medications

Peripherally (at the nociceptor) Cannabinoids, NSAIDs, Opioids, Tramadol, Vanilloid receptor antagonists (i.e., capsaicin)

Peripherally(along the nociceptive nerve)

Local anaesthetics, Anticonvulsants (except the gabapentinoids)

Centrally(various parts of the brain)

Acetaminophen, Anticonvulsants (except the gabapentinoids), Cannabinoids, Opioids, Tramadol

Descending inhibitory pathwayin the spinal cord

Cannabinoids, Opioids, Tramadol, Tricyclic antidepressants, SNRIs

Dorsal horn of the spinal cord Anticonvulsants, Cannabinoids, Gabapentinoids, NMDA receptorantagonists, Opioids, Tramadol, Tricyclic antidepressants, SNRIs

AUTONOMIC NERVOUS SYSTEM

AUTONOMIC NERVOUS SYSTEM Controls most visceral functions of the body Rapidity & intensity with which it changes

functions Activated by centres located in spinal cord,

brain stem, & hypothalamus 2 major subdivisions-PARASYMPATHETICSYMPATHETIC

SYNAPSE

SYMPATHETIC SYSTEM

SYMPATHETIC SYSTEM Also called thoracolumbar system:

all its neurons are in lateral horn of gray matter from T1-L2

Lead to every part of the body (unlike parasymp.)

Norepinephrine ( noradrenaline) is neurotransmitter released by most postganglionic fibers (acetylcholine in preganglionic) “adrenergic”

PARASYMPATHETIC SYSTEM

PARASYMPATHETIC SYSTEM

Also called the craniosacral system because all its preganglionic neurons are in the brain stem or sacral levels of the spinal cord Cranial nerves III,VII, IX and X In lateral horn of gray matter from S2-S4

Only innervate internal organs (not skin) Acetylcholine is neurotransmitter at end

organ as well as at preganglionic synapse “cholinergic”

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ADRENAL GLAND

On top of kidneys

Adrenal medulla (inside part) is a major organ of the sympathetic nervous system

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ADRENAL GLAND Synapse in gland Can cause body-wide

release of epinephrine/adrenaline and norepinephrine in an extreme emergency(adrenaline “rush” or surge)

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Summary

HOMOEOSTASIS

CORE TEMPERATURE

The core temperature of the human body is 37°C The core of the human body includes the organs

of the thorax, abdomen and the head This is where the vital organs are located Their enzyme systems must operate in optimum

conditions The periphery of the body can withstand some

deviation from the core temperature

HEAT LOSS AND HEAT GAINThe body must balance its heat budgetHeat is gained: by conduction from warm air surrounding the body by the body’s metabolic activity which generates heat

e.g. when muscle moveHeat is lost: by conduction and radiation to cold air (or water) by evaporation of sweat from the body surface

(c.f. properties of water) Humans can also affect their body temperature by

changing their behavioure.g. wearing different clothes, seeking shade

MAINTAINING THE BODY TEMPERATURE

Keeping warm Staying cool

Increased insulation, subcutaneous fat reduces the conduction of heat from the body

Increase blood flow to skin, increases conduction and radiation of heat from the body

Reduced sweating decreases evaporation

Increased sweat secretion, increases evaporation

Increased shivering, increases heat produced by muscle tissue 2 to 5 times

Reduced activity

© 2008 Paul Billiet ODWS

nerves

Less heat generated

More water covers the skin.

More evaporation

Skin arteries dilateMore blood to the

skin. More radiation & conduction of heat

Muscles of skin arteriole

walls relaxSweat glands

increase secretion

Musclesreduce activity

Core body temperature

>37°C

Hypothalamus

Thermoreceptors

Thermoreceptors

Return to 37°C

Muscles of skin

arteriole walls relax

Core body temperature

>37°CHypothalamus

Sweat glands

increase secretion

nerves

Musclesreduce activity

Thermoreceptors

NEGATIVE FEEDBACK

Blood temperature

Body loses heat

nerves

More heat generated

Less water covers the skin.

Less evaporation

Skin arteries constrict

Less blood to the skin.

Less radiation & conduction of heat

Muscles of skin arteriole

walls constrict

Sweat glands

decrease secretion

Musclesshivering

nerves

Core body temperature

<37°C

Thermoreceptors

Hypothalamus

Thermoreceptors

Return to 37°C

NEGATIVE FEEDBACK

Blood temperature

Body loses less heat

Body gains heat

Muscles of skin

arteriole walls

constrict

Core body temperature

<37°C

Sweat glands

decrease secretion

nerves

Musclesshivering

Thermoreceptors Hypothalamus

nerves

OVERVIEW -TEMPERATURE HOMEOSTASIS

IN HUMANS

NERVE INJURIES

Epineurium

Perineurium

Endoneurium

Fascicles

Nerve fiber

Node of Ranvier

Schwann cellMyelin

Axon

TRAUMA TO PERIPHERAL NERVES Interruption of nerve trunk (neurotmesis) Interruption of axons (axonotmesis) Total conduction failure (neurapraxia) Impaired conduction (no morphologic

change)

CAUSES OF INJURY TO PERIPHERAL NERVES Trauma Compression (entrapment) Irritation Metabolic disorders Inflammatory (neuritis) Virus Age related changes

Axon

EpineuriumPerineuriumEndoneurium

Neurapraxia

NEURAPRAXIA Caused by pressure for a short period Axon not destroyed No function loss Recovers spontaneously over days or weeks

(when the cause is resolved) Results of spontaneous recovery are almost

always good

AXONOTMESIS

Severe prolonged pressure Wallerian degeneration Nerve may regenerate from injured location away

from the cell body Regeneration: 1 mm per day (approx. 1 inch per

month) Results of spontaneous recovery are good to

moderate depending on distance

NEUROTMESIS

Does not regenerate spontaneously Grafting is necessary to restore function Results of grating are good to moderate to failures Of three types- 3rd degree- endoneurium interrupted 4th degree- epineurium and perineurium also

interrupted 5th degree-complete transection of the nerve trunk

Injured nerves

Axon interrupted(Wallerian degeneration)

Interruption of axon andendoneurial sheet

Interruption ofperineurial sheet

Interruption of nerve trunk

INTERRUPTED AXONS

Degenerate distally (away from cell body) Wallerian degeneration Interrupted axons regenerate from injury, provided

that endoneural tube is intact

BIBLIOGRAPHY GUYTON’S TEXTBOOK OF PHYSIOLOGE MALAMED’S LOCAL ANAESTHESIA MONHEIM’S LOCAL ANAESTHESIA ROWE & WILLIAMS VOLUME 2

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