Disorders of the

Autonomic Nervous System

Althea P. Tampos, M.D.

Physiologic and Pharmacologic Considerations:

1.
2.
3.

Has only sympathetic postganglionic fibers:

Sweat glands
Cutaneous blood vessels
Hair follicles

1.

Only preganglionic sympathetic innervation:

Adrenal medulla

Neurohumoral Transmission

Neurohumoral Transmission
Acetycholine (Ach)

Terminals of all preganglionic fibers

Skeletal muscle fibers
All postganglionic parasympathetic fibers:
Receptors:
1.
Nicotinic skeletal muscles; blocked by tubocurarine
2.
Muscarinic innervated organs; antagonized by
atropine
Some postganglionic sympathetic (sweat glands)

Neurohumoral Transmission

Noerpinephrine (NE) postganglionic sympathetic fibers

Adrenergic receptors
1. Alpha vasoconstriction, relaxation of gut, dilation of pupils
1. Alpha1 postsynaptic
2. Alpha 2 presynaptic, decrease release of transmitters
2. Beta vasodilation, relaxation of bronchi, increased heart
rate and contractility
1. Beta 1 increases heart rate and contractility
2. Beta 2 relaxes smooth muscles of bronchi, blood
vessels of skeletal muscles

1.

Central Regulation
Brainstem
1.

Nucleus tractus solitarius main visceral afferent

1.
2.

3.

CN X (nodose ganglion)
CN IX (petrosal ganglion)

carry cardiovascular, respiratory and GI afferents,

baroreceptor and chemoreceptor info.
Caudal subnuclei main receiving site for viscerosensory
fibers, receives baroreceptor and chemoreceptor info.

Projects to hypothalamus, amygdala, insular cortex,

pontine and medullary nuclei

Central Regulation
2. Cerebrum
1.

Hypothalamus integrates ANS and limbic system via:

1.
Direct pathway
1.
Ventromedial prefrontal (temperature, sweating)
2.
Cingulate cortices - voluntary control of bladder and
bowel
3.
Insular cortex cardiac arrythmias, alteration of
visceral functions
4.
Limbic lobe visceral brain
2.
Pituitary endocrine glands

Regulation of Blood Pressure

Baroreceptors (afferent components)

Sensitive to decrease in pulse pressure
1.
Carotid sinus rapidly responsive, responds to beat-to-beat
changes
2. Aortic arch longer response time, discriminate only larger and
more prolonged alterations in pressure
Alterations in blood volume
1. Right heart chamber
2. Pulmonary vessels
Afferent fibers CN IX and X; motor nucleus of vagus nerve
Terminal ganglion nucleus of tractus solitarius
Main sympathetic flow via greater splanchnic nerve to celiac
ganglion
Renal Juxtaglomerular cells release renin which stimulates
angiotensin production and influence aldosterone producion

Regulation of bladder function

Parasympathetic innervation
S2-S4
Muscarinic acetycholine receptors of detrusor muscles
Sympathetic innervation
Detrusor muscle
T10-T12
From inferior mesenteric ganglia through hypogastric
nerve to pelvic plexus
Supplies beta adrenergic receptors at bladder dome
Internal sphincter
Alpha receptors
Internal sphincter and base of basal trigone
External urethral and anal sphincter innervated by pudendal
nerve from S2-S4; Ventrolateral part of Onufs nucleus

Central regulation of bladder functions:

Micturition centers:
1.
Pontomesencephalic tegmentum
2.
Frontal lobe ( paracentral region)

Examination of ANS

Postural Hypotension

Fall in BP of >30mmHg systolic and 15mmHg diastolic

Increase heart rate
Failure of above responses vagal dysfunction

Bladder Function Test

cystometogram

Tests for vasomotor function:

Cold pressor test

immerse hand in cold water for 1 5 min

Increase systolic BP to 15-20 and diastolic BP to 10 -15
mmHg

Sustained isometric contraction test

Normal skin temperature : 31-33 C

Hand grip for 5 min

Increase HR and BP

Test for GI function

Barrium swallow

Test for sudomotor functions

Galvanic skin resistance test

Lacrimal function

Schirmer test Normal: wet area in filter paper is15 mm

If < 15 mm suggest keratoconjunctivitis

Acute Autonomic Paralysis

Dysautonomic Polyneuropathy
Pure Pandysautonomia
Both sympathetic and parasympathetic systems are
affected mainly at postganglionic level
Somatosensory and motors fibers are spared
Idiopathic
(+) antibodies against ganglionic acetylcholine
receptors

1.
2.
3.
4.
5.
6.

7.

Signs and symptoms:

Anhidrosis
Orthostatic hypotension
Paralysis of pupillary reflexes
Loss of lacrimation and salivation
Impotence
Impaired bladder and bowel dysfunction (urinary
retention, postprandial bloating, ileus or
constipation)
Loss of pilomotor or vasomotor responses in skin
(flushing and heat intolerance)

Treatment:

IVIg
Plasma exchange

Variants:

Sympathetic orthostatic hypotension

Postural orthostatic tachycardia syndrome

Idiopathic Orthostatic Hypotension

Degenerative disease of middle and late adult life
Lesions involve

1.
2.
3.
4.

mainly postganglionic sympathetic neurons

Preganglionic lateral horn neurons of thoracic and spinal
horn neurons degenerate

Signs and symptoms:

Orthostatic hypotension
Impotence
Anhidrosis
Atonicity of bladder

2 types (multiple system atrophy):

1.

Postganglionic type

NE is decreased in supine and standing position because

of failure of damaged nerve terminals to synthesize or
release catecholamines

Central type

2.
1.

2.

Striatonigral degeneration or Shy-Drager syndrome

autonomic failure was associated with Parkinsonian
syndrome and cytoplasmic inclusions in sympathetic
neurons
Olivopontocerebellar degeneration involves stiatum,
cerebellum,pons and medulla

Treatment:
Sleep with elevation of head
Mineralocorticoids:

Fludrocortisone acetate
Midrodine

Elastic/compression stockings

Peripheral Neuropathy With

Secondary Orthostaic Hypotension

Acute and chronic peripheral neuropathies affect

autonomic fibers
Diabetes, alcoholic-nutritional, amyloid, GBS, heavy
metal and toxic neuropathies
Hyponatremia maybe secondary to release of antidiuretic hormone

Diabetic Neuropathy

Impotence
Constipation
Diarrhea (especially at night)
Hypotonia of bladder
Gastroparesis
Orthostatic hypotension
Sensory polyneuropathy
Argyll-Robertson pupils

Pathophysiology
Vacuolization of sympathetic ganglionic neurons
Cell necrosis and inflammation
Loss of myelinated fibers in vagi and white rami
communicantes
Loss of lateral horn cells in spinal cord

Riley-Day Syndrome

Familial disease in children (autosomal recessive)

Postural hypotension and lability of blood pressure
Faulty regulation of temperature
Diminished hearing
Hyperhydrosis
Blotchiness of skin
Insensitive to pain
Emotional lability
Cyclic vomiting
Hypoactive tendon reflexes

Pathophysiology:

Deficiency of neurons in superior cervical ganglion and

lateral horn of spinal cord

Mutation in gene IKAP

Failure of embryonic migration or formation of first and

second order sympathetic neurons

Autonomic Failure in Elderly

65 years and above

Orthostatic hypotension
Lability of temperature
Loss of sewating of lower parts of body and
increased sweating of head and arms
Impotence and incontinence

Horner or Oculosympathetic
Syndrome
Triad:

1.

2.
3.

Ptosis
Miosis
Anhydrosis

Pathophysiology includes interruption of:

postganglionic sympathetic fibers along internal carotid

artery
superior cervical ganglion
preganglionic fibers between their origin in
intermediolateral horn cells (C8-T2) spinal segments and
superior cervical ganglion
Descending , uncrossed hypothalamospinal fibers in
tegmentum of brainstem

1.

2.
3.
4.

5.

Common causes:
Neoplastic or inflammatory involvement of cervical
lymph nodes or proximal part of brachial plexus
Surgical or trauma to cervical structures
Carotid artery dissections
Syringomyelia or trauma of second thoracic spinal
segments
Infarcts or other lesions of lateral part of medulla

Other manifestations:

Heterochromia iridis
Harlequin effect

Ross syndrome

Combination of segmental anhidrosis and Adie pupil

Sympathetic and Parasympathetic

Paralysis in Tetraplegia and Paraplegia

Complete lesion in C4/C5 and upper thoracic (above

T6)
Usual causes:

Traumatic necrosis of spinal cord

Infarction
Necrotic myelitis
Tumors

Acute cervical cord transection abolished

sensorimotor, reflex, and autonomic functions of
spinal cord

Spinal shock:
Acute cervical cord transection abolished
sensorimotor, reflex, and autonomic functions
of spinal cord
Hypotension
Loss of sweating

Piloerection
Paralytic ileus and gastric atony

Paralysis of bladder
Decrease plasma epinephrine and
norepinephrine

Mass reflex

Flexor spasms of legs and involuntary

emptying of bladder are associated with:
marked rise in BP
Bradycardia
Sweating
pilomotor reactions in parts below cervical
segment (autonomic dysreflexia)

Autonomic crises

Sympathetic storm
Abrupt over activity of sympathetic and
parasympathetic nervous systems hypertension
and midriasis coupled with signs of CNS
excitation
Maybe caused by drugs as:

Phenylpropanolamine
Tricyclic antidepressants

Cocaine
Cholinergic blockers

Tricyclic anti-depressants

Dryness of mouth
Flushing
Ventricular arrhythmia

absent sweating
mydriasis
paralysis

Rodenticied (PNU)

Tetanic spasms
Midriasis

diaphoresis
sustained hypertension

Severe head injury with hypertensive cerebral

hemorrhage

Syndromes of unopposed sympathetic-adrenal medullary

hyperactivity
Mechanisms:
1.

2.

3.

Outpouring of adrenal catecholamines with acute

hypertension and tachycardia
Cushing response brainstem mediated vasopressor reaction
(hypertension, bradycardia, slow, irregular breathing)
Extreme hypertension, profuse diaphoresis, pupillary
dilatation usually arising during diencephalic autonomic
seizures

Myocardial abnormalities maybe due to norepinephrine

and cortisol surge

Disorders of Sweating

Hyperhydrosis:

Results from overactivity of sudomotor nerve

Botulinum toxin

Interruption of postganglionic sympathetic

fibers

Raynaud Syndrome

Episodic, painful blanching of fingers probably due

to digital artery spasm
Age of onset: 14 years
Pallor, cyanosis, and rubor discoloration of fingers
or toes
Brought about by cold or emotional stress
Numbness, paresthesias, burning sensation
Maybe associated with connective tissue diseases:
scleroderma, rhematoid disease
Maybe due to obstructive arterial disease, minor
trauma

Treatment:

Avoidance of cold exposure

Drugs that an cause vasoconstriction ( clonidine)
Calcium channel blockers (nifedipine)

Disturbances of bladder function

complete destruction of cord below T12

No awareness of state of fullness, voluntary initiation of

micturition is impossible; bladder distends as urine
accumulates until there is overflow incontinence, voiding
is possible only by Crede maneuver, saddle aneshesia,
loss of bulbocavernosus and anal reflexes as well as
tendon reflexes

Disease of sacral motor neurons in spinal gray

matter, anterior sacral roots or peripheral nerves
innervating the bladder

Same as in I but sacral and bladder sensations are intact

Frontal lobe incontinence

Nocturnal enuresis

Supranuclear hyperactivity of detrusor and precipitant

evacuation

Urinary incontinence during sleep

Delay in acquiring inhibition of micturition

Interruption sensory afferent fibers from bladder

Therapy of disordered micturition:

Bethanicol for flaccid bladder paralysis; contracts

detrusor by stimulating its muscarinic cholinergic
receptors
Propatheline, atropine for spastic bladder paralysis; act
as muscarinic antagonist
Alpha1synpathomimetic blocking drugs (terazosin,
doxazosin) relax urinary sphincter and facilitate voiding
Intermittent catheterization
Implantation of sacral anterior root stimulator

Disturbances of Bowel Function

Congenital Megacolon ( Hirschsprung Disease)

Affects mainly male infants and children

Congenital absence of ganglionic cells in the myenteric
plexus
Often involves internal anal sphincter and rectosigmoid
Most serious complication: enterocolitis and has high
mortality