Autonomic Nervous System

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Autonomic Nervous System

• RICHARD E. FREEMAN MD MPH
• 2013
• Lock Haven University

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NERVOUS SYSTEM - REVIEW
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HOMEOSTASIS

• The bodys ability to maintain a stable,
  relatively constant condition through multiple
  dynamic equilibrium adjustment and regulation
  mechanisms.

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Divisions of the Nervous System
Location
Direction
Control
Action
Structures
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NEUROTRANSMITTER

• Neurotransmitters endogenous chemicals that
  transmit signals from a neuron to a target cell
  (FREQUENTLY another neuron or muscle) across a
  synapse.
• Examples Acetylcholine, epinephrine,
  norepinephrine, serotonin, dopamine etc

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THE SYNAPSE
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COMING AND GOING

• AFFERENT
• ARRIVING from the SENSORS to THE CENTRAL NERVOUS
  SYSYTEM
• INCOMING
• EFFERENT
• EXITING from the THE CENTRAL NERVOUS SYSTEM to
  the EFFEXORS
• OUTGOING
• ALL NERVES IN THE AUTONOMIC NERVOUS SYSTEM ARE
  EFFEFENT

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GANGLION VS PLEXUS

• Ganglia mass of neuron cell bodies that
  interconnect and relay info via synapses
• Dorsal Root ganglia afferent (sensory)
• Autonomic ganglia efferent (motor)
• Basal ganglion Brain-relay stations for multiple
  cerebral/cerebellar/thalamic/hypothalamic/brain
  stem functions
• Examples striatum, caudate nucleus, globus
  pallidum, substantia nigra, etc
• Plexus intersecting and recombining nerve
  fibers- (major highway intersections)

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AGONIST VS. ANTAGONIST

• An agonist is a chemical that binds to cell
  (neuroreceptor) triggers or stimulates a
  response by that cell.
• Example Epinephrine Beta receptor stimulate-
  speeds up the heart
• An antagonist blocks the action of an agonist
  either by blocking the receptor or causing the
  inverse (opposite) action of the agonist.
• Example Metoprolol Beta Blocker- slows the
  heart rate

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Somatic versus Autonomic Pathways

• ANS 2 neurons span the distance from CNS to
  effectors
• presynaptic neuron cell body in CNS -- brain or
  spinal cord
• postsynaptic neuron cell body in a peripheral
  ganglion (not dorsal root ganglion)

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AUTONOMIC- GENERAL PROPERTIES
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General Properties of the ANS

• Motor (EFFERENT)system that controls visceral
  organs
• glands, cardiac and smooth muscle
• Regulates unconscious processes that maintain
  homeostasis
• ANS carries out its actions without our intent
• INVOLUNTARY

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TWO Divisions of the ANS

• SYMPATHETIC DIVISION
• prepares body for physical activity
• (Flight or Fight)
• PARASYMPATHETIC DIVISION
• calming affect on many body functions assists
  in bodily maintenance
• (Rest and Digest)

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Central Control of Autonomic Function

• ANS is regulated by several levels of the CNS
• Limbic system connected to hypothalamus
• Hypothalamus
• (major visceral motor control center)
• Reticular formation brainstem nuclei
• Spinal cord reflexes
• WILL BE MORE SPECIFIC LATER!!

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Visceral Reflexes

• Unconscious, automatic responses to stimulation
• 1. Receptors detect internal stimuli -?
• 2. Afferent neurons (incoming) connect to
  interneurons (connecting) in the CNS?
• 3. Interneurons synapse with efferent neurons
  (outgoing)
• 4. Efferent neurons carry motor signals to the
  effectors
• EFFECTORS
• GLANDS,
• SMOOTH MUSCLE,
• CARDIAC MUSCLE,

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Visceral Reflex Arc
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EXAMPLEVisceral Reflex to BLOOD PRESSURE
CHANGES
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AUTONOMIC TONE

• AUTONOMIC TONE
• normal rate of activity that represents the
  BALANCE of the two systems
• Goal Maintain Homeostasis
• ACCELERATOR AND BRAKE
• Effects of each system depend upon
  neurotransmitters released

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Sympathetic and Parasympathetic Tone

• the BASAL AND BALANCED rate of activity of each
  system
• this background activity allows for an increase
  or decrease in activity by a single system
• EXAMPLES
• sympathetic tone normally causes about
• 50 vasoconstriction
• increasing or decreasing tone can change vessel
  diameter
• parasympathetic tone provides background G.I.
  activity

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Sympathetic Tone and Vasomotor Tone
Sympathetic division prioritizes blood vessels to
skeletal muscles heart in times of emergency.
Blood vessels to skin vasoconstrict to minimize
bleeding if injury occurs during stress or
exercise.
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Dual Innervation

• Most of viscera receive nerve fibers from both
  parasympathetic sympathetic divisions
• antagonistic effects oppose each other
• cooperative effects seen when 2 divisions act on
  different effectors to produce a unified effect
• Example Sexual response
• Parasympathic Gets it up Erection
• Sympathetic Gets it out - Ejaculation
• Normally, both divisions do not innervate an
  organ equally

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Control WITHOUT Dual Innervation

• Adrenal medulla, arrector pili muscles, some
  sweat glands many blood vessels receive only
  sympathetic fibers
• Sympathetic tone is a baseline firing frequency
• Vasomotor tone can shift blood flow from one
  organ to another according to changing needs

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SYMPATHETIC NERVOUS SYSTEM
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NEUROTRANSMITTERS OF THE SYMPATHETIC SYSTEM

• Preganglionic (short fiber)
• Acetylcholine (Nicotinic)
• Postganglionic (long fiber)
• Norepinephrine
• Acetylcholine (rarely)

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Pathways of Preganglionic Sympathetic Fibers
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Efferent Pathways of Sympathetic NS
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Collateral Ganglia Abdominal Aortic Plexus
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Adrenal Glands Sympathetic ganglia

• Paired glands sit on superior pole of each kidney
• Cortex
• Mineralcorticoids aldosterone
• Glucocorticoids cortisol
• Androgens testosterone
• Medulla catecholamines
• Sympathoadrenal system
• the closely related functioning adrenal medulla
  and Symphathetic NS
• EPINEPHRINE, NOREPIPHRINE DOPAMINE
• ALL ACT LIKE HORMONES

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Stress Response

• mass sympathetic discharge
• increase in arterial pressure, heart rate and
  contractility, blood flow to muscles, blood
  glucose, metabolic rate, muscle strength, mental
  activity, blood coagulation
• prepares the body for vigorous activity need to
  deal with a life-threatening situation
• AKA - the fight or flight response

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Summary of Sympathetic Innervation

• BODY WALL
• Effectors are innervated by sympathetic fibers
  found in spinal nerves (mixed with afferent
  fibers)
• FREQUENTLY travel WITH SOMATIC NERVES
• Piloerector muscles, sweat glands, vessels
• HEAD AND THORACIC CAVITY
• Effectors are innervated by fibers in sympathetic
  nerves
• FREQUENTLY travel WITH CRANIAL NERVES
• ABDOMINAL CAVITY
• Effectors are innervated by sympathetic fibers
  in splanchnic nerves.

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Summary of the end organ (effector) response to
Sympathetic stimulation

• Apocrine/eccrine glands Increased secretions
• Eyes
• Pupillary Dilation
• Lacrimal Slight Increased secretion
• Endocrine
• Adrenal cortex Increased secretion
• Adrenal medulla Increased secretion
• Digestive
• Gallbladder Relaxation
• Intestine Decreased peristalsis
• Internal anal sphincter Contraction (pucker
  up!!)
• pancreatic glands Decreased secretion
• salivary gland Decreased secretion
• Lungs
• Bronchial muscles Dilation
• Bronchial secretions Reduced production
• Cardiovascular
• Coronary arteries, Dilation (beta) Constriction
  (alpha)
• skeletal muscle vessels, Dilation (beta)
  Constriction (alpha)

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PARASYMPATHETIC SYSTEM
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Parasympathetic Nervous System

• Division of Autonomic NS
• Functions in harmony (opposition) to SNS
• Regulates visceral organs
• SLUDGE salivation, lacrimation, urination,
  defecation, GI functions, emesis
• Pre and postganglionic neurons synapse close to
  the organ of innervation (unlike the SN where the
  ganglion is typically farther away from the
  target organ).

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Efferent Pathways of Parasympathetic NS
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Parasympathetic Functions of Cranial Nerves

• Oculomotor nerve (III)
• Facial nerve (VII)
• Glossopharyngeal (IX)
• Vagus nerve (X)

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Vagus Nerve
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Summary of the end organ effect of the
Parasympathetic stimulation

• Apocrine/eccrine glands No action
• Eyes
• Pupillary Constriction
• Lacrimal Greatly increased secretion
• Endocrine
• Adrenal cortex No action
• Adrenal medulla No action
• Digestive
• Gallbladder Contraction
• Intestine Increased peristalsis- defecation
• Internal anal sphincter Relaxation
• pancreatic glands Greatly increased secretion
• salivary gland Greatly increased secretion
• Lungs
• Bronchial muscles Constriction
• Bronchial secretions Greatly increased
• Cardiovascular
• Coronary arteries, No action
• skeletal muscle vessels, No action

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Autonomic nervous system-neurotransmitters
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Neurotransmitters Receptors

• Types of neurotransmitters released and types of
  receptors on target cells determines effects of
  ANS
• Sympathetic NS has longer lasting effects
• Many other substances also released as
  neurotransmitters
• enkephalin, substance P, neuropeptide Y,
  neurotensin, nitric oxide

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Cholinergic Receptors for ACh

• Acetylcholine binds to 2 classes of receptors
• nicotinic receptors (cholinergic receptor)
• Between pre and postganglionic neurons of BOTH
  sympathetic and parasympathetic NS
• muscarinic receptors (cholinergic receptor)
• Between postganglionic neurons and target organ
  in ALL parasympathetic neurons
• Between some postganglionic neurons and target
  organs in sympathetic NS

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ACETYLCHOLINE

• CHOLINESTERASE

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RASEHIBITORS
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NICOTINIC RECEPTORSFUNCTION

• A key function of nicotinic receptors is to
  trigger rapid neural and neuromuscular
  transmission. OPENING Na Channels?RAPID
  DEPOLARIZATION AND REPOLARIZATION

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NICOTINIC RECEPTORSLOCATION

• Nicotinic receptors are found in
• The somatic nervous system
• (neuromuscular junctions in skeletal muscles).
• BOTH sympathetic and parasympathetic nervous
  system (autonomic ganglia)
• .POST GANGLIONIC NEURON
• The central nervous system

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CLINICAL FINDINGS NICOTINIC RECEPTOR
STIMULATIONSYMPATHETIC NERVOUS SYSTEM

• (due to ganglionic stimulation of the adrenal
  gland).
• Hyperglycemia, glycosuria, ketosis.
• Hypertension.
• Leukocytosis with a left shift.
• Mydriasis (pupillary dilation) in up to 13 of
  the cases.
• Sweating.
• Tachycardia, tachydysrhythmias.
• Urinary retention.

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NICOTINIC RECEPTOR STIMULATION(CHOLINESTERASE
INHIBITOR)

• Monday Mydriasis (pupillary dilation)
• Tuesday Tachycardia
• Wednesday Weakness
• Thursday Hypertension
• Friday Fasciculations

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MUSCARINIC RECEPTORSMUSHROOM POISON

• Muscarinic receptors are located in the
• PARASYMPATHETIC NERVOUS SYSTEM.
• Cardiac conduction system.
• Exocrine glands.
• Smooth muscles.
• Sympathetic nervous system.
• Sweat glands.
• Central nervous system.

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MUSCARINIC RECEPTORS

• Slower BUT response is prolonged
• May be excitatory or inhibitory.
• Do not affect skeletal muscles
• Do influence the activity of smooth muscle,
  exocrine glands, and the cardiac conduction
  system.
• MODULATE ONLY- DO NOT INITIATE (due to intrinsic
  electrical/mechanical rhythmic activity)

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MUSCARINIC RECEPTORS

• No channels Receptor activates guanine
  nucleotide binding protein (G-protein)? activates
  many intracellular activities

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MUSCARINIC ACTIONS

• CARDIAC EFFECTS.
• AV blocks, with escape rhythms.
• Bradycardia.
• Ventricular dysrhythmias.
• EXOCRINE GLAND ACTIVITY.
• Bronchorrhea.
• Hyperamylasemia.
• Lacrimation.
• Rhinorrhea.
• Salivation.
• SMOOTH MUSCLE ACTIVITY.
• Bladder stimulation, sphincter relaxation.
• Bronchospasm.
• Miosis (pupillary constriction), eye pain due to
  ciliary spasm.
• Nausea, vomiting, cramps, diarrhea

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Parasympathetic (muscurinic)TOXIDROMESLUDGE DU
MBELS

• Salivation Defecation/Diaphoresis
• Lacrimation Urination
• Urination Miosis (pupillary constriction)
• Defecation Bronchospasm and Bronchorrhea
• GI pain Emesis
• Emesis Lacrimation
• Salivation

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NEUROTRANSMITTERS OF THE SYMPATHETIC NERVOUS
SYSTEM- ADRENERGICS (catecholamines)

• NOREPINEPHRINE
• HORMONE NEUROTRANSMITTER
• Post ganglionic sympathetic neurons
• Adrenal medulla

• EPINEPHRINE
• HORMONE NEUROTRANSMITTER
• Adrenal medulla

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Adrenergic Receptors for NE

• Norepinephrine binds to 2 classes of receptors
• Alpha (adrenergic)
• Beta (adrenergic)
• Beta 1
• Beta 2

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Adrenergic Receptors and Function

• Alpha
• Vasoconstriction
• Iris Dilation
• Intestinal relaxation
• Pilomotor contraction
• Bladder Sphincter Contraction

• Beta
• Vasodilation
• Cardioacceleration
• Increased myocardial strength
• Uterus relaxation
• Bronchodilation
• Glycogenolysis
• Bladder wall relaxation

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END ORGAN EFFECTS OF AUTONOMIC STIMULATION OR
INHIBITION
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EYE

• SYMPATHETIC --pupillary dilation (mydriasis)
• Meds phenylephrine, cocaine, epinephrine
• PARASYMPATHETIC--pupillary constriction and
  accommodation (focusing) of the lens
• Meds pilocarpine muscarinic receptor
• GLAUCOMA

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Dual Innervation of the Iris
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GLANDS OF THE BODY

• SYMPATHETIC
• stimulates the sweat glands
• PARASYMPATHETIC
• stimulate the nasal, lacrimal, salivary, and G.I.
  gland

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GI TRACT

• SYMPATHETIC
• has very little effect
• PARASYMPATHETIC
• stimulates overall activity including G.I. smooth
  muscle

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Enteric Nervous System

• Nervous system of the digestive tract
• Composed of 100 million neurons found in the
  walls of the digestive tract (no components found
  in CNS)
• Has its own reflex arcs
• Regulates motility of viscera and secretion of
  digestive enzymes and acid in concert with the
  ANS peristalsis - sequential

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Enteric Nervous System
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HEART

• SYMPATHETIC
• increases the rate and contractility
• systemic (adrenal medulla) epinephrine/norepinep
  hrine and some direct
• SA Node
• PARASYMPATHETIC
• decreases heart rate
• Vagus Nerve-cholinergic
• AV node

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BLOOD VESSELS

• SYMPATHETIC
• Vasoconstriction-arterioles
• Raises blood pressure
• PARASYMPATHETIC
• some vasodilation

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SECTION PHARMOCOLOGY THE AUTONOMIC NERVOUS
SYSTEM
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ADRENERGIC OR SYMPATHOMIMETIC AGONISTS

• act like norepinephrine and epinephrine
• these drugs have an effect which is much more
  prolonged than that of either norepi or epi
• Phenylephrine/oxymetolazine stimulates alpha
  receptors
• Isoproterenol, stimulates both beta1 and beta2
  receptors
• albuterol stimulates only beta2 receptors
• some drugs act indirectly by increasing the
  release of norepi from its storage terminals
• ephedrine, tyramine, and amphetamine

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ADRENOGENIC ANTAGONIST SYMPATHOLYTIC

• drugs that block (antagonist) the effect of
  norepi and epi antagonist
• synthesis and storage
• reserpine
• release from the nerve terminal
• guanethidine
• alpha blockers
• phentolamine and phenoxybenzamine
• Prazosin (Minipress) Blood pressure
• Terasosin (Hytrin) - alpha-1 blocker- BPH
• beta blockers
• beta1 and 2 - propranolol, beta1 - metoprolol
• ganglionic blockers
• hexamethonium

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ANS pharmacology

• PARASYMPATHOMIMETIC DRUGS
• nicotine
• activates nicotinic receptors
• pilocarpine and methacholine
• activates muscarinic receptors, cause profuse
  sweating
• CHOLINESTERASE INHIBITORS
• Donepezil (Aricept) Rivastigmine (Exelon)
  Alzheimers
• neostigmine, pyridostigmine,and ambenonium
• potentiates the effect of acetylcholine
• ANTIMUSCARINIC DRUGS
• atropine and scopolamine
• blocks the effect of acetylcholine on effector
  cells

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• . Nicotinic and muscarinic receptors (Choose ALL
  correct answers)A. Are both acetylcholine
  receptors.B. Have the same structure.C. Have
  different physiology.D. Have different
  functions.E. None of the above.

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• When compared with the action of nicotinic
  receptors, muscarinic receptors (Choose ALL
  correct answers)A. Are faster.B. Initiate
  rather than modulate smooth muscle activity.C.
  Have primarily parasympathetic effects on the
  peripheral nervous system.D. Stimulate sweating
  via the sympathetic nervous system.E. None of
  the above.

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• Muscarinic receptors are found in (Choose ALL
  correct answers)A. Skeletal muscle.B. Smooth
  muscle.C. Exocrine glands.D. Sweat glands.E.
  None of the above.

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• . Cholinesterase inhibitor toxicity leads to the
  following clinical findings mediated by
  muscarinic receptors (Choose ALL correct
  answers)A. Miosis (pupillary constriction).B.
  Bronchorrhea.C. Nausea.D. Bronchospasm.E. None
  of the above.