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A. Anatomy of the ANSnavigator

  1. ANS neurons are located in ganglia outside of the central nervous system (CNS)
  2. Carried By Types B and C Fibers [2]
    1. Type B are preganglionic autonomic fibers, <3.0µm wide, 3-15 meters/sec conduction
    2. Type C are postganglionic autonomic fibers, 0.4-1.3µm wide, 0.3-2.3 m/sec conduction
  3. CNS regulation of ANS
    1. CNS integrates information and produces an output
    2. CNS efferents to the ANS are preganglionic
    3. All preganglionic neurons use acetylcholine (ACh) as neurotransmitter
    4. CNS neurons controlling ANS also use dopamine (DA)
    5. DA neurons in CNS also partially control sympathetic norepinephrine (NE) neurons
  4. Ganglionic ANS neurons give rise to post-ganglionic axons which innervate the body
    1. ANS neurons are divided into sympathetic and parasympathetic types
    2. Sympathetic neurons use NE as the major neurotransmitter
    3. Postganglionic sympathetic neurons to the eccrine sweat glands use ACh
    4. Parasympathetic (postganglionic) neurons use ACh
  5. Sympathetic
    1. "Fight" or "Flight"
    2. Increased blood vessel tone, heart rate, sweating response
    3. Interface with adrenal medulla, which produces epinephrine (Epi)
    4. NE is produced from DA which is made from L-DOPA
    5. Main metabolite of NE is dihydroxyphenylglycol (DHPG), which is found in blood
    6. Assessment of sympathic ANS accomplished using blood levels of NE, L-DOPA, DHPG
  6. Parasympathetic
    1. Homeostatic controls
    2. Non-threatining situations
    3. Normal exocrine, endocrine, gastrointestinal and other functions
  7. Synthesis of ANS Neurotransmitters
    1. Tyrosine is converted to Dopa via tyrosine hydroxylase
    2. Dopa converted to DA via L-aromatic aminoacid decarboxylase
    3. NE is synthesized from DA via DA ß-hydroxylase (DBH)
    4. Acetylcholine is produced from choline via choline acetyltransferase

B. Systems Controlled by ANSnavigator

  1. Cardiovascular
  2. Gastrointestinal Motility
  3. Genito-urinary Function
  4. Temperature Regulation
  5. Endocrine Glands
  6. Exocrine Glands
  7. Body Fluid Composition

C. Centers Regulating Autonomic Functionnavigator

  1. Hypothalamus (Temperature Set Point, ADH, others)
  2. Locus Ceruleus
  3. Dorsal Motor Nucleus of Vagus (CN X; Parasympathetics)
  4. Intermediolateral Column (Sympathics)
  5. Onef's Nucleus

D. Cardiovascular (CV) System [10] navigator

  1. Maintenance of Blood Pressure (BP)
    1. Prevents hypotension which can lead to inadequate major organ perfusion
    2. Maintenance of BP on standing to prevent orthostatic changes
    3. Control of heart rate is discussed elsewhere
  2. BP Regulation
    1. Sympathetic response with Epi (adrenal glands) and NE (neural control)
    2. Sympathetics also lead to increased heart rate
    3. Parasympathetics (vagal) to lower heart rate
    4. Parasympathetic acetylcholine generally leads to vasodilation
    5. Extrapyramidal system secretes dopamine (renal and cardiovascular effects)
    6. Upregulation of inducible nitric oxide synthetase in sepsis syndrome triggers apoptosis of neurons in cardiovascular ANS and exacerbates hypotension [3]
  3. Afferent
    1. Baroreceptors
    2. Found in carotid sinus, aortic arch
    3. Parasympathetic afferents via CN IX and X (vagus) to brainstem
  4. Efferents
    1. Efferent parasympathetics via vagus
    2. Efferent sympathetics via intermediolateral horn using NE at nerve terminations
    3. These efferent sympathetics use nicotinic acetylcholine receptors at ganglia
    4. In normal persons, NE levels nearly double when going from sitting to standing
    5. Adrenergic receptor sensitivity also plays a role in regulating autonomic BP changes
  5. Adrenomedullary System
    1. Adrenal medulla is composed of post-ganglionic neurons (neural crest derived)
    2. Production of Epi (mostly ß-adrenergic) and NE (alpha and ß-adrenergic)
    3. Body's critical stress response
    4. Epi is the first "counter-regulatory" (anti-insulin) hormone produced
    5. Insulin causes hypoglycemia and this is countered through the efferent ACh pathway
    6. The body responds to hypoglycemia with increased ACTH and high sympathetic outflow
  6. Orthostatic Intolerance
    1. Syndrome with adrenergic symptoms occur when upright posture is assumed
    2. Heart rate increases >29 beats per minute without orthostatic hypotension
    3. Most patients are women 20-50 years old
    4. Previously called "Soldier's Heart", neurocirculatory asthenia, mitral valve prolapse syndrome
    5. Abnormal cerebrovascular regulation found in some orthostatic intolerant patients [4]
    6. Norepinephrine transporter deficiency may be present in some patients [5]
    7. Dopamine ß-hydroxylase (DBH) deficiency leads to orthostatic hypotension [6]
    8. DBH deficiency has elevated plasma DA and lack of plasma NE levels
    9. DBH deficiency responds well to L-threo-3,4 dihydroxylphenylserine, which converts to NE [6]
  7. ANS Dysregulation in Disease
    1. Essential Hypertension (neurogenic) - elevated NE levels
    2. Panic Disorder
    3. Orthostatic hypotension (neurogenic)
    4. Congestive Heart Failure (CHF)
    5. Chronic Fatigue Syndrome

E. Gastrointestinal (GI) Systemnavigator

  1. Parasympathetics
    1. Innervation via vagus nerve and pelvic sacral nerves
    2. Increase GI smooth muscle tone, enhances peristalsis
    3. Relax GI sphincters
    4. Acethylcholine (ACh) stimulates exocrine gland secretion
    5. ACh also stimulates secretion of gastrin, secretin, and insulin
  2. Sympathetics
    1. Inhibits GI motility
    2. Relatively minor role in maintenance of normal GI homeostasis
  3. Generalized Motility Disorders [7]
    1. Achalasia due to failed innervation (parasympathetic) of lower esophagus
    2. Hirschprung's Disease due to failed innervation (parasympathetic) of distal colon
    3. Hyperganglionosis - neuronal dysplasia, ganlioneuromatosis (MEN Syndrome 2B)
    4. Hypoganglionosis - usually acquired (Chagas' Disease, Paraneoplastic Syndromes)
  4. Diabetic GI (mainly gastric) dysmotility is less common than originally believed [8]

F. Erectile Function [9] navigator

  1. Erection (tumescence) is due to engorgement of corpora cavernosa with blood
  2. Complex interplay of central (cerebral, spinal) and local factors
    1. Local factors are smooth muscle (SmM) and endothelium
    2. Interplay of vasodilator and vasoconstrictor mechanisms
  3. Usual flaccid state of penis results from contraction of arterial and corporal SmM
    1. This contraction is mediated by alpha2-adrenergic neurons (sympathetic)
    2. Contracted arterial and corporal SmM lead to limited penile blood supply
  4. Erection occurs when the SmM relax
    1. Resistance of penile arterioles and cavernosal sinusoids decreases
    2. This allows >3 fold increase in blood flow into corpus cavernosa
    3. Decrease in adrenergic tone occurs
    4. Parasympathetic neurons are main central conduits for initiation of vasodilation
  5. Mechanisms of Vasodilation
    1. Vasodilation due mainly to nitric oxide (NO) along with some prostaglandins
    2. Nitric oxide works through cGMP, blocking calcium uptake
    3. PGE1 inhibits calcium uptake by a different mechanism
    4. Vasoactive intestinal polypeptide (VIP) also plays a role in vasodilation
  6. Engorgement of sinusoids leads to compression in subtunical venous plexus
    1. This leads to reduction in venous outflow
    2. Both increased inflow and reduced outflow maintain an erection
  7. Detumescence is due to a reversal of these events mediated mainly by NE

G. Autonomic Function Testing (Panel 2, Ref [2])navigator

  1. Cardiac Parasympathetic Nervous System Function
    1. Heart-rate variability with deep respiration
    2. Heart-rate response to valsalva maneuver
    3. Heart-rate response to standing (30 to 15 ratio)
  2. Sympathetic Adrenergic Function
    1. Blood pressure response to upright posture (standing or tilt-table)
    2. Blood pressure response to Valsalva maneuver
  3. Sympathetic Cholinergic Function
    1. Thermoregulatory sweat testing
    2. Quantitative sudomotor-axon-reflex test
    3. Sweat imprint methods
    4. Sympathetic skin response

References navigator

  1. Goldstein DS, Robertson D, Esler M, et al. 2002. Ann Intern Med. 137(9):753 abstract
  2. Freeman R. 2005. Lancet. 365(9466):1259 abstract
  3. Sharshar T, Gray F, de la Grandmaison GL, et al. 2003. Lancet. 362(9398):1799 abstract
  4. Jacob G, Atkinson D, Jordan J, et al. 1999. Am J Med. 106(1):59 abstract
  5. Shannon JR, Flattem NL, Jordan J, et al. 2000. NEJM. 342(8):541 abstract
  6. Gomes MER, Deinum J, Timmers HJLM, Lenders JWM. 2003. Lancet. 362(9392):1282 abstract
  7. Goyal RK and Hirano I. 1996. NEJM. 334(17):1106 abstract
  8. Jones KL, Russo A, Berry MK, et al. 2002. Am J Med. 113(6):449 abstract
  9. Korenman SG. 1998. Am J Med. 105(2):135 abstract
  10. Freeman R. 2008. NEJM. 358(6):615 abstract