55 yr old male

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• 55 yr old male
• k/c/o Multiple System Atrophy with Neurogenic
  Orthostatic Hypotension had supine hypertension
• Treated with an anti-hypertensive
• Developed erectile failure
• Depressed ! ! !

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Went to a doctor

• Prescribed a tricyclic antidepressant
• Patient was still depressed
• Over the counter took a aphrodisiac
• Developed severe headache
• BP 220 / 140 mm Hg
• And DIED .

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WHY ?

• Possibly due to harmful interaction b/w
  aphrodisiac and drugs used to treat autonomic
  failure syndrome
• Tricyclics block neuronal reuptake of
  norepinephrine
• Aphrodisiac ( yohimbine ) releases norepinephrine
  from sympathetic nerves
• This combination increases norepinephrine
  delivery to its receptors
• In the setting of baroreflex failure, the
  NE-induced increase in BP is unopposed and lethal
  .

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Autonomic Nervous System Basic Anatomy
Physiology
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Introduction

• The critical component of central network
  involved in homeostasis adaptation
• 3 subdivisions
• Sympathetic Nervous System
• Parasympathetic Nervous System
• Enteric Nervous System

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• Peripheral Autonomic Network
• Central Autonomic Network

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Peripheral Autonomic Network
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Anatomical Functional Organization

• Sympathetic Parasympathetic efferent pathways
  carry signals from brain to periphery.
• Consisting of 2 neurons
• Pre ganglionic neuron
• Autonomic ganglion that innervates target organ

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• Pre ganglionic neurons send myelinated axons to
  peripheral autonomic ganglia and to enteric
  nervous system.
• Neurons of the sympathetic or parasympathetic
  ganglia send unmyelinated axons ( post ganglionic
  axons ) that innervate heart, smooth muscle and
  exocrine glands.
• Peripheral parasympathetic ganglia are located
  close to target organs and send short axons to
  innervate these visceral effectors.

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Sympathetic System

• Sympathetic preganglionic neurons are primarly
  located in intermediolateral nucleus at the T1 to
  L2 levels of spinal cord
• Distribution of preganglionic fibers does not
  follow dermatomal pattern of somatic nerves.

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• Preganglionic sympathetic axons exit through
  ventral roots and pass via white rami
  communicantes on corresponding spinal nerve to
  reach the paravertebral sympathetic chain
• Majority of them run rostrally or caudally along
  the sympathetic chain and synapse on large
  paravertebral ganglia.
• Remaining fibers pass through paravertebral chain
  without synapsing and form splanchnic nerves that
  innervate prevertebral ganglia adrenal glands

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• Paravertebral sympathetic ganglia primary relay
  stations for preganglionic inputs
• They innervate all tissues and organs except
  those in abdomen, pelvis and perineum
• Eg superior cervical ganglion
• stellate ganglion
• prevertebral ganglion

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Superior Cervical Ganglion

• Sends postganglionic axons that follow branches
  of carotid arteries
• Innervate eye, facial sweat glands, salivary
  glands, blood vessels of face brain, pineal
  gland, thyroid and parathyroid glands
• Elicit pupil dilatation
• contraction of muller muscle
• facial sweating
• vasoconstriction-facialcerebral
  circulation
• complex effects on salivary
  lacrimal secretion

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Stellate Ganglion

• Recieves preganglionic inputs from T2 T6
  segments
• It sends postganglionic axons that join
  peripheral nerve via gray rami communicantes
  follow the distribution of corresponding somatic
  nerve to innervate blood vessels and sweat glands
  in upper limbs trunk
• Elicit vasoconstriction / vasodilatation in skin
  and muscle, sweating, piloerection

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Stellate Ganglion

• Stellate ganglion together with other cervical
  ganglion thoracic ganglia provides input to
• esophageal plexus,
• pulmonary plexus,
• cardiac plexus.
• Elicit cardiac acceleration
• bronchodilatation

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Prevertebral Ganglia

• Located anterior to abdominal aorta
• close to origin of celiac mesenteric
  arteries
• Innervate all abdominal, pelvic perineal organs
• Preganglionic input from spinal seg T5 L2 are
  carried by splanchnic nerves to celiac and
  superior mesenteric ganglia
• Provide postganglionic fibers to celiac plexus
  that innervates all abdominal viscera except
  descending colon and rectum
• Outputs vasoconstriction , inhibition of GI
  MOTILITY

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• Preganglionic axons from spinal seg L1 L2
  travel in lumbar splanchnic nerves
• Synapse in inferior mesenteric ganglion
• Provide axons to hypogastric plexus innervating
  descending colon, rectum, bladder sexual organs
• Elicit vasoconstriction
• smooth muscle relaxation
• constriction of internal sphincters
  of
• bladder and
  rectum
• ejaculation

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• The prevertebral sympathetic ganglia integrate
  preganglionic with afferent inputs from dorsal
  root and enteric nervous system
• And they innervate the viscera and blood vessels
  of the abdomen and pelvis .

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Parasympathetic System

• Parasympathetic outputs arise from preganglionic
  neurons located in nuclei of the brain stem
  sacral spinal cord
• Preganglionic parasympathetic axons travel a long
  distance before eventually reaching their target
  ganglia which are located close to or even within
  the target end organs

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• Cranial preganglionic parasympathetic nuceli
  project via CN III, VII, IX, X
• Westphal nucleus is a part of occulomotor complex
  in midbrain sends preganglionic axons that
  occupy peripheral portion of the occulomotor
  nerve and synapse on the neurons of ciliary
  ganglion in the orbit
• These neurons innervate iris and ciliary muscles
• Eliciting pupil constriction
• accomodation of eye

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• Superior salivatory nucleus
• In pons
• projects via facial nerve to sphenopalatine
  ganglion, which innervates -
• lacrimal gland ( lacrimation )
  cerebral blood
  vessels ( vasodilatation )
• to submandibular ganglion
• secretomotor vasodilator inputs to
  corresponding salivary glands

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• Inferior salivatory nucleus
• In medulla
• Sends axons via glossopharyngeal nerve
• Synapse on Otic ganglion
• Stimulate parotid gland secretion

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• Most preganglionic parasympathetic output from
  brain stem is mediated by Vagus nerve
• Vagus innervates heart, respiratory tract and
  entire gastrointestinal tract except descending
  colon and rectum
• Most vagal preganglionic neurons situated in
  dorsal motor nucleus of vagus
• provides input to git and respiratory tracts ,
  heart
• Vagal preganglionic output to heart -
  Neurons in ventrolateral portion of
  nucleus ambiguus
• Vagus cardioinhibitory, visceromotor and
  secretomotor effects

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• Sacral preganglionic output
• Arises from neurons of sacral preganglionic
  nucleus located in lateral gray matter of spinal
  segments S2 S3
• Their axons pass via ventral roots of pelvic
  splanchnic nerves which join inferior hypogastric
  plexus
• Innervate colon, bladder, sexual organs
• Parasympathetic output contraction of bladder
  detrussor muscle circular smooth muscle of
  rectum.

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• Sacral parasympathetic output elicits
• Vasodilatation of cavernous tissue of penis
• required for penile erection ,
• whereas sympathetic output controls
  ejaculation

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Enteric Nervous System

• Consists of sensory neurons, interneurons and
  motor neurons located in the myenteric and the
  submucosal plexus within the walls of the gut
• They form local reflex circuits that mediate
  motility, secretion and blood flow throughout gut
• Also the inputs from vagus and prevertebral
  ganglia modulate it .

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Visceral Afferents

• Inform CNS about Mechanical Chemical events in
  internal organs
• This information is conveyed to produce conscious
  visceral sensation and initiate visceral reflex
  responses
• Spinal visceral afferents innervate all
  peripheral organs
• Their cell bodies are in dorsal root ganglion

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• Brain stem visceral afferents are carried
  primarily by glossopharyngeal and vagus nerves
• Cell bodies in petrosal nodose ganglia
• All brain stem visceral afferent nerves relay in
  nucleus of solitary tract ( NTS )
• NTS is a major site of information integration of
  many bodily functions

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• Rostral portion of NTS receives taste afferents
  via facial nerve( geniculate ganglion ) ,
• glossopharyngeal vagus nerves
• Intermediate portion receives gastrointestinal
  afferents
• Caudal portion of the NTS recieves afferent
  information from baroreceptors, cardioreceptors,
  chemoreceptors and pulmonary receptors

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Neurochemical Transmission

• Cholinergic Transmission
• Adrenergic Transmission

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Cholinergic Transmission

• Ach - neurotransmitter in
  
• all pre-ganglionic neurons,
• parasympathetic ganglion neurons,
• sympathetic neurons innervating sweat glands,
• most enteric nervous system neurons
• Effects of Ach are mediated by Nicotinic and
  Muscarnic Receptors

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Adrenergic Transmission

• With exception of the sweat glands ,
  Norepinephrine is the primary neurotransmitter in
  sympathetic ganglionic neurons
• Epinephrine is released from chromaffin cells of
  adrenal medulla and acts as a circulating hormone
• Norepinephrine Epinephrine act via Alpha1,
  Alpha2, Beta receptors
• Smooth muscle contraction Alpha1 receptors
• Stimulation of heart Beta1 receptors
• Smooth muscle relaxation Beta2 receptors
• Lipolysis in brown fat Beta3 receptors

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Denervation Supersensitivity

• In response to loss of innervation by
  postganglionic sympathetic or parasympathetic
  axons there is increased responsiveness of
  visceral target organ to neurotransmitter or
  agonist that stimulates adrenergic / muscarnic
  receptors.
• Leads to exagerrated pressor responses to
  adrenergic agonists.
• Indicates a postganglionic lesion

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Lets see a case ?
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• A 65 yr old male
• h/o Diabetes mellitus
• admitted for severe headache
• On ex Pulse 90 / min
• BP 180/100 mm Hg
• patient had no h/o HTN ,
• but had respiratory infection and took
  decongestant pseudoephedrine 1 hour prior to
  development of symptoms

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This a case of.

• Diabetic autonomic neuropathy with denervation
  supersensitivity !!!
• Affecting adrenergic vasomotor fibers which
  leads to up-regulation of vascular Alpha1
  -adrenergic receptors
• Here even a minimal blood levels of alpha1
  agonist ( pseudoephedrine) lead to exagerrated
  pressor responses.

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Other Peripheral Autonomic Neurotransmitters

• ATP
• Nitric oxide
• Neuropeptide Y
• Substance P
• Calcitonin gene related peptide

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Physiology
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Sympathetic Outflow

• Sympathetic preganglionic neurons organized
  into different functional units which control
  specific targets
• Muscle vasomotor
• Splanchnic vasomotor
• Skin vasoconstrictor
• Skin vasodilator
• Cardiomotor
• Visceromotor preganglionic neurons

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• Sympathetically induced vasoconstriction of
  skeletal muscle and splanchnic vessels is
  critical to avoid orthostatic hypotension ( alpha
  1 )
• Sympathetic outflow to skin blood vessels and
  sweat glands is critical for thermoregulation
• exposure to cold skin vasoconstriction
• piloerection (
  alpha 1 )
• exposure to heat sweating
• skin
  vasodilatation ( M3 )

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Parasympathetic Outflow

• Main brain stem parasympathetic outflow is
  mediated by vagus nerve
• Has cardioinhibitory effect ( M2)
• It is critical for beat to beat control of heart
  rate
• Constriction of bronchial smooth muscle
• Stimulate bronchial gland secretion
• Normal motility of oesophagus and stomach (M3)
• Facilitatory role in intestinal motility

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• Sacral parasympathetic is critical for
• micturition ( M3 )
• defecation ( M3 )
• penile erection ( NO )
• Nociceptive Visceral afferents
• substance P, tachykinin A, CGRP

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Enteric Nervous System

• Includes several types of sensory neurons,
  interneurons, motor neurons which form
  integrative local reflex circuits
• Controlling motility, secretion, blood flow
  throughout the gut
• The activity of enteric nervous system is largely
  independent of extrinsic innervation but is
  modulated by both
  vagal inputs
  from dorsal vagal nucleus and
  sympathetic inputs from prevertebral ganglia

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Another Case
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• 55 yr old male
• k/c/o insulin dependent diabetes mellitus
• c/o light headedness upon standing
• particularly early morning and after
  eating
• h/o nausea after eating
• h/o constipation , erectile dysfunction
  
• On ex
• Pupils fail to dilate in dim light
• Weakness of foot dorsiflexors
• Absent ankle jerks
• Loss of all sensation modalities below mid calf
• Postural hypotension

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• Autonomic lab tests
• impaired sudomotor axon reflex response
• reduced variation of heart rate to deep
  breathing
• reduced valsalva ratio
• orthostatic hypotension
• gi motility delayed gastric emptying
• usg post void urine 250 cc

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• A CASE OF DIABETIC AUTONOMIC NEUROPATHY
• Sympathetic failure orthostatic hypotension
• impaired
  sweating
• abnormal BP
  during valsalva
• Vagal impairment delayed gasstric emptying
• constipation
• reduced
  variability of hr
• urinary
  retention
• erectile
  dysfunction

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Central Autonomic Network
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Components

• Telencephalic structures insular cortex
• ant
  cingulate cortex
• 
  amygdala
• - integration of bodily sensation, emotion,
  decision making
• - anterior cingulate cortex motivation,
• 
  goal directed behavior
• - amygdala conditioned fear responses

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• Hypothalamus central role in integrating
  autonomic and endocrine responses
• Hypothalmus critical role in adaptation to
  internal / external stimuli, while maintaining
  homeostasis
• 3 zones
• Paraventricular zone neuroendocrine control via
  connections to pituitary
• Medial zone thermoregulation, osmoregulation,
  food intake, response to stress
• Lateral zone arousal behaviour, sleep wake cycle

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• Brain Stem Components
• Periaqueductal gray
• integration of autonomic, somatic and
  antinociceptive responses to external stress.
  
• coordinates cardiovascular, respiratory,
  thermoregulatory, urinary, reproductive and pain
  control systems
• Parabrachial nucleus taste, salivation, gi
  activity, cardiorespiratory activity,
  thermoregulation
• NTS 1st relay center for taste and visceral
  afferent information carried in CN VII,IX,X
• And also for all medullary, cvs, rs, gi
  reflexes

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Autonomic dysreflexia

• Interruption of descending inputs to
  preganglionic sympathetic neurons by lesions
  above T5 level may lead to unpatterned excessive
  sympathoexcitation in response to visceral /
  somatic stimuli
• Eg severe hypertension in response to bladder
  distention or other peripheral inputs

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Baroreceptor reflex

• Powerful moment to moment negative feedback loop
  that regulates arterial blood pressure .
• It minimizes fluctuations in arterial pressure
  during standing, exercise or emotion

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• RISE IN BP
• DISTENSION OF BLOOD VESSEL
• MECHANOSENSITIVE BARORECEPTORS SITTING IN WALLS
  OF CAROTID SINUS AND AORTIC ARCH
• Afferent information travels from
• carotid baroreceptors in glossopharyngeal n
• aortic arch baroreceptors in vagus
• To NTS
• 3 BARORECEPTIVE PATHWAYS FROM NTS

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• 1. Projections to cardiac vagal neurons - HR
• 2. Neurons in VLM inhibit sympathetic outflow
  
• to decrease peripheral vasomotor tone
• 3. Ascending projections to Supraoptic and
• Paraventricular nuclei to inhibit
  vasopressin
• release.
• THE COMBINATION OF BRADYCARDIA PERIPHERAL
  VASODILATATION RESTORES BLOOD PRESSURE

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Thank you HAPPY NEW YEAR