Download Autonomic Nervous System

Autonomic Nervous System
Anatomy & Physiology
Diseases & Evaluation
2014
John Kincaid MD
Origin of Concepts
• In the 2nd century A.D. Galen concluded that nerves were tubes
which distributed “animal spirits” throughout the body
• The coordination of body functions by these tubes and spirits was
“sympathy”
• 1700’s: Winslow used the term Sympathetic for the chain of nerves
running parallel to the spinal cord
• Late 1800’s & early 1900’s: Langley & Gaskell defined the
“Visceral” nervous system to consist of Sympathetic,
Parasympathetic & Enteric components
• Langley’s concept was an Efferent system only
• Langley suggested Autonomic as a substitute for visceral or
vegetative Autonomic: auto = self nomos = law
Langley” 3 Autonomic
Divisions:
•Sympathetic
•Parasympathetic
•Enteric
•The Sympathetic division
was the
“Thoraco-Lumbar”
•The Parasympathetic division
was the “Cranio-Sacral”
•The Enteric division was intrinsic
to the GI system
Rhoades 2nd ed
Fig 6-4
Sympathetic action is done by a two neuron chain:
•Preganglionic neuron (1st order) & Postganglionic neuron (2nd order)
•Preganglionic neurons
arise from the
intermediolateral
column of the spinal cord
between T1 & L3
•Postganglionic neurons
arise from the
paravertebral or
prevertebral ganglia in the
abdomen
Low 1st ed Fig 1-1
•Preganglionic sympathetic axons exit a spinal nerve to a sympathetic ganglia via a
“white ramus”
•Synapse with postganglionic neurons may occur at that or higher/lower spinal levels
•Most postganglionic neurons rejoin the spinal nerve via the “gray ramus” to
cutaneous, vascular & muscle targets in the trunk & limbs
•Preganglionic axons to intra-abdominal structures go through paravertebral ganglia
to prevetebral ganglia
•Sympathetic function
tends to “diverge”
•One preganglionic neuron
may synapse with up to 100
postganglionic neurons
Parasympathetic action also uses a two neuron chain
•Preganglionic neurons arise from brainstem nuclei & the sacral spinal cord
•Postganlionic neurons arise in ganglia located on or in the target structures
•Parasympathetic action tend to be less divergent than sympathetic
Low 1st ed Fig 1-3
Anatomical Issues
How do sympathetic
axons get from Th1 to
the eye OR from L3 to the
bottom of the foot?
Where are the
parasympathetic ganglia
for the heart ,lungs,
intestines, and bladder?
What is the parasympathetic
role in cutaneous functions?
How do sympathetic axons get
to the heart & lungs?
Cardiac Autonomic Pathways
Cardiac sympathetic
output via “cardiac nerves”
• Superior, middle &
inferior cervical ganglia
• Upper 3 thoracic levels
Haines, 2nd ed
Autonomic Neurotransmitters
•Acetylcholine is the
transmitter at preganglionic
synapses in both systems
•The receptor is similar to the
neuromuscular junction
synapse: directly gated
channel which responds to the
agonist nicotine
•The postganglionic
parasympathetic transmitter
also is acetylcholine
•The receptors are indirectly
gated and respond
to the agonist muscarine
Rhoades 2nd ed Fig 6-2
The neurotransmitter at postganglionic SYMPATHETIC synapses is
norepinephrine
( with one exception )
•The receptor is an
indirectly gated G protein
linked type
•There are 2 general subtypes
of postganglionic norepinephrine
synapses: alpha & beta
•These two synapses use
different 2nd messenger systems
& respond to different
agonists ADD Stuff
•The exception to
norepinephrine is the
sweat glands whose
postganglionic neurons
release acetylcholine
Adrenal Medulla
•
•
•
•
•
The adrenal medulla is the
“macro” nerve terminal of the
sympathetic system
Preganglionic axons pass through
the paravertebral ganglia to
terminate directly on the
chromaffin cells of the adrenal
medulla
These cells release
neurotransmitters directly into the
circulation
The output is 80% epinephrine
The effect of vascular delivery
lasts 5x longer than by release
from postsynaptic nerves
nd
Non-adrenergic Non-cholinergic
Neurons (NANC)
• Some autonomic neurons
release Nitric Oxide (NO)
instead of norepinephrine or
acetylcholine
• NO releasing parasympathetic
neurons innervate the corpus
cavernosa of the penis
• Nitric oxide release stimulates
production of cyclic GMP &
vasodilatation in the corpus
• Phosphodisterase type 5
breaks downs GMP
• Sildenafil or CIAlis inhibits this
enzyme & enhances local
vascular “performance”
• Neuropeptides & autonomic fx
Autonomic Functions
Effector
Pupil
Sweat glands
Blood vessels
Skin
Muscle
Heart rate
Bronchioles
Parasymp
Symp
Constrict
None
Dilate
Secrete
None (face)
None
Decrease
Constrict
Constrict*
Constrict*
Increase
Dilate
Autonomic Functions
Effector
GI tract
wall muscles
Glands
Urinary system
Detrusor
Sphincter
Genitalia
Parasymp
Symp
Contract
Secrete
Relax
Inhibit
Contract
Relax
Relax
Contract
Engorge
Contract
Gastrointestinal Control
• The Enteric nervous
system in walls of GI tract
can function semiindependently
• Effects: motility, secretion
& blood flow
• Autonomic action can
influence these activities
• Efferent and afferent
components ( 90% of
vagal axons are sensory)
Vago-vagal reflexes
Low, Clinical Autonomic Disorders 3rd ed
Gastrointestinal Control
• Parasympathetic GI input
is mostly above the small
intestine & below the
transverse colon
• Sympathetic input is more
widespread
• Parasympathetic action
increases motility &
secretion
• Sympathetic action
inhibits motility &
secretion increases local
blood
Barfing flow
Low, Clinical Autonomic Disorders 3rd ed
Bladder Control
• Parasympathetic input via
Pelvic Splanchnic nerves
Bladder wall (detrusor)
Internal Sphincter
• Sympathetic input via
Hypogastric Nerves
• Somatic input via
Pudendal Nerve
Voluntary sphincter
• Afferent components
Autonomic Nerves Wilson-Pauwels
1997 Fig CS 4-1
Bladder Control
Pontine Micturaton Center
Bladder Filling
• Sympathetic action inhibits
bladder wall contraction &
enhances internal sphincter
contraction
Bladder Emptying
• Sympathetic output is inhibited
• Sensory input is allowed to
activate parasympathetic
mediated contraction of the
detrusor & relaxation of
internal sphincter
• Pudendal somatic activity to
the voluntary sphincter is
inhibited
• Disease effects
Mathias & Bannister
Central Autonomic Network
• Cortical areas: Insular,
anterior cingulate,
prefrontal
• The amygdala & lateral
hypothalamus are the
conduits for emotion
related input
• The suprachiasmatic &
medial hypothalamic
nuclei regulate circadian
& homeostatic functions
Mathias & Bannister 4th ed
Thermoregulation
Hypothalamic zones
• Medial preoptic nuclei:
warm sensing neurons
which initiate heat
dissipation
• Dorsomedial & posterior
nuclei: cold sensing
neurons which initiate
shivering and metabolic
heat production
• Both project to medullary
raphe region
Haines Fundamental Neuroscienc 30-6
Central Autonomic Network
• The periaqueductal gray
matter receives efferent
input from the
hypothalamus
• Afferent input is via the
Nucleus Tractus
Solitarius (NTS)
• The ventral-lateral
medulla is the origin of
efferent parasympathetic
& sympathetic activity
• The intermediolateral cell
column of the spinal cord
is the efferent pathway
for sympathetic activity
Central Autonomic Network
Afferent input via:
• Nucleus of the Solitary Tract
(NTS) via Facial, glossopharyngeal
& vagal axons from:
taste buds on tongue
baroreceptors (carotid & aortic
sinuses)
chemoreceptors ( carotid body),
pulmonary and cardiac stretch
receptors
• Spinal cord from: visceral,
•
Low Clinical Autonomic Disorders 3rd ed
thermo, ergo & nociceptic
receptors
Afferent data passes via spinal
nerves & spinothalamic tract to
thalamus & to insular cortex
Efferent Actions
• Ventrolateral Medulla
is efferent path for:
vasomotor tone (S)
cardiac regulation (P &S)
respiratory drive (Som)
GI regulation (P & S)
• Ventral medullary raphe
is sympathetic pathway to
sweat gland (sudomotor)
& vasomotor control to
the skin
Low, Clinical Autonomic Disorders 3rd ed
Blood Pressure & Cardiac Control
• Ventral lateral medulla
regulates blood pressure
& heart rate responses to
orthostatic, exercise &
emotional challenges
• Baroreceptor (BR) reflex
is the main pathway for
this control
• Transmitters: Glutamate
& Gaba
Fig 4.3 Low, Clinical Autonomic Disorders 3rd ed
Blood Pressure & Cardiac Control
BRs are mechanosensitive
endings in carotid & aortic
sinuses
• Continous discharge
pattern which ↑ in systole
& ↓ in diastole
• Sustained ↑ in BP ↑ BR
discharge rate which then
Inhibits output of RVLM to
spinal sympathetic
neurons &
Enhances vagal (nucleus
ambiguus) output to the
heart
Blood Pressure & Cardiac Control
BR reflex allows us to stand up
without fainting
• Upright posture shifts ~500 ml
of blood to the lower body
• ↓ venous return & ↓ cardiac
output unloads BRs
• ↓ vagal & ↑ sympathetic output
via BR reflex maintains BP &
cardiac output
• In first 15-30 sec post standing
BP is supported by ↓ vagal
output resulting in ↑ heart rate
• At 1-2 minutes post standing
sympathetic output ↑ to
maintain pressure
Mechanism of Syncope
Normals have 20 mm or less drop in systolic BP
after 2 minutes of standing
Autonomic Dysfunction
• Ocular: Impaired adjustment to lighting levels
• Secretomotor: Dry Eyes or Mouth
• Orthostatic: Dizziness, weakness, exercise
intolerance & syncope when upright
• Enteric: Bloating, early satiety, nausea,
constipation, diarrhea
• Urological: Impaired emptying, incontinence
Autonomic Dysfunction
•
•
•
•
Sexual: Erectile & ejaculatory dysfunction
Sudomotor: Deficient or excess sweat output
Vasomotor: Skin color & temperature dysfx
Endocrine: Hypoglycemic unawareness
Autonomic Dysfunction
Primary Diseases
• Multi-system atrophy (Shy Drager)
• Pure Autonomic Failure ( Idiopathic orthostatic
hypotension)
• POTS (Postural Orthostatic Tachycardia Syndrome)
• Primary hyperhydrosis
Secondary Conditions
•
•
•
•
•
•
Diabetic Neuropathy
Amyloidosis
Acute Pandysautonomia ( GBS variant)
Lambert Eaton Syndrome
Hypohydrosis ( Ross syndrome)
Neuro-cardiogenic Syncope
Autonomic Dysfunction
Postural Orthostatic Tachycardia Syndrome
(POTS)
• Heart rate ↑ > 30 bpm or to > 120 bpm within 10 minutes
of standing
• Orthostatic BP Δ within normal range
• Orthostatic intolerance symptoms
• Female / Male 5:1 most pts 20-40 yrs
• ? Post-viral etiology in some
Autonomic Dysfunction
POTS
•
•
•
•
•
•
Possible pathologic mechanisms
Excessive sympathetic tone
Excessive venous pooling (limb denerv)
β receptor supersensitivity
α receptor hyposensitivity
Altered parasympath / sympath balance
Brain stem dysregulation
Autonomic Evaluation
Pupillary responses to light & dark
Tear & Salivary output
BP maintenance during standing for 2-3 minutes / Check BP & HR
Early responses (Parasympathetic withdrawl) ↑ HR
Later Response (Sympathetic increase)
• As blood pools in legs cardiac return ↓
• Sympathetic response constricts capacitance blood vessels, ↑ HR &
leg muscle contraction
• Response max @ ~ 2 minutes
• BP should ↓ < 20 mm systolic ( < 10 mm diastolic)
• HR should ↑ > 10-20
Tilt table testing eliminates leg muscle contraction component of
orthostatic response
Autonomic Testing
Evaluation of the Orthostatic Response
• In normals HR ↑ by ~ 15 sec and then ↓ by ~ 30
sec after standing
• 30 : 15 ratio: Longest to Shortest RR interval in
1st 30 beats after standing
< ~1.15 is abnormal
This component of the orthostatic response is
vagally mediated: reduction in parasympathetic
output to the heart with resulting ↑ HR
Autonomic Testing
Valsalva Maneuvre
Mathias & Bannister 4th ed Fig 21.6
• Abrupt sustained ↑ intra
thoracic pressure: 40
mmHg blow for 15 sec
while sitting
• Immediate HR ↓ at onset
& gradual ↑ until pressure
released & then reflex
bradycardia occurs
• Valsalva ratio is HR @1 /
HR @ 2
• Nl > ~ 1.3
• Cardiovagal
(parasympathetic) test
Cardiovascular – Valsalva Maneuver
280
120
Wolfgang Singer Mayo Rochester
240
80
Heart rate
40
160
0
Systolic BP
120
-40
Diastolic BP
80
-80
40
-120
0
10
20
30
40
50
60
70
80
Parasympathetic and Sympathetic
components
Time (sec)
90
100
110
HR (bpm)
BP (mmHg)
200
Autonomic Evaluation
Hear rate Δ with respiration
Mathias & Bannister 4th ed Fig
• In normal respiration HR
↑ during Inspiration & ↓
during Expiration
• Normal “sinus arrythmia”
• Do 10 cycles of 6/minute
respiration while
assessing HR
• I:E Normal Δ 10-15 BPM
• Cardiovagal
(parasympathetic) test
Autonomic Evaluation
Sudomotor (Sweat) function
• Temperature sensing
• Hypothalamic control
• Sympathetic (cholinergic)
output
• Sweat production
Evaluate by:
• Heating whole body &
assess sweating pattern
TST (thermoregulatory
sweat test)
OR
Low ,Clinical Autonomic Disorders 2nd ed Ch19, Fig 3
Autonomic Evaluation
•Locally applied stimului: Quantitative Sudomotor
Axon Test: QSART
Low, Clinical Autonomic Disorders 2nd
Methodology
• Ach locally
iontophoresed into
the skin
• Sweat glands
activated
• Sweat out put
ed Ch 15, Fig 3
measured
Autonomic Evaluation
QSART Patterns
RSD &
Neuropathic pain
Low, Clinical Autonomic Disorders 2nd ed Ch 15 Fig 4
Fig 3
Autonomic Evaluation
• What we are currently doing @ IU Health