ILS 6: Autonomic Nervous System

preganglionic neuron cell body is in

CNS [brainstem or spinal cord]

postganglionic neuron cell body is in

autonomic ganglion in PNS

preganglionic neuron is short in

SNS

preganglionic neuron is long in

PNS

postganglionic neuron is short in

PNS

postganglionic neuron is long in

SNS

Parasympathetic [craniosacral] preganglionic neurons originate from

• brainstem nuclei of cranial nerves III, VII, IX, X

• sacral spinal cord segments S2-S4

sympathetic [thoracolumbar] preganglionic neurons originate from

spinal cord segments T1-L2

postganglionic neuron cell bodies of both parasympathetic & sympathetic divisions are in

autonomic ganglia

ANS primarily uses which neurotransmitters?

ACh

NE

Adrenergic neurons

• release NE

• most sympathetic postganglionic neurons

Cholinergic neurons

• release ACh

• all preganglionic sympathetic & parasympathetic neurons

• all postganglionic parasympathetic neurons

Sympathetic postganglionic neurons innervate

• smooth muscles of some BV’s in skeletal muscle

• sweat glands

• piloerector muscles

*release ACh unlike other postganglionic sympathetic nerves that release NE

intermediolateral [IML] cell column of lateral horn

contains cell bodies of preganglionic fibers of SNS

anterior [ventral] root

axons of SNS preganglionic fibers leave via this structure & enter sympathetic trunk thru the white communicating ramus

• carry myelinated fibers

gray communicating ramus

• carry SNS postganglionic fibers originating from sympathetic ganglion

• carry unmyelinated fibers

• join spinal nerves

Celiac ganglion

sympathetic

• liver, gallbladder, stomach, duodenum, pancreas, spleen, & small intestine

Aorticorenal ganglion

sympathetic

• kidneys, adrenal glands, superior portion of ureter, & gonads

superior mesenteric ganglion

sympathetic

• proximal large intestine

inferior mesenteric ganglion

sympathetic

• distal 1/3 of transverse colon, descending colon, sigmoid colon, & rectum

Adrenal medulla

• specialized sympathetic ganglion

• preganglionic sympathetic fibers synapse directly on chromaffin cells

chromaffin cells

• modified postganglionic sympathetic neurons

• secrete catecholamines [80% EPI, 20% NE] directly into bloodstream

superior cervical ganglion [SCG]

• largest paravertebral ganglion

• supplies BVs & cutaneous targets of face, scalp, & neck

• innervates pupillary dilator muscle, superior tarsal muscle, salivary glands, lacrimal glands, & BVs

• interruption of the sympathetic pathway thru the SCG → Horner Syndrome

stellate ganglion

fusion of inferior cervical & 1st thoracic [T1] ganglia

• provides sympathetic fibers to head, neck, upper limbs, & heart

Catecholamines

EPI

NE

Dopamine [DAD]

• from dopaminergic neurons

Mechanism of synthesis of catecholamines

NE synth begins in nerve endings of SNS

1. tyrosine → L-DOPA

   1. enzyme: tyrosine hydroxylase [rate-limiting step]

2. L-DOPA → Dopamine

   1. enzyme: DOPA decarboxylase

3. Dopamine → transported into synaptic vesicles

   1. transporter: vesicular monoamine transporter [VMAT]

4. Dopamine → NE

   1. enzyme: dopamine beta-hydroxylase

5. NE → EPI

   1. enzyme: phenyl ethanolamine N-methyltransferase [PMNT]

   2. occurs primarily in chromaffin cells of adrenal medulla

catecholamines are synthesized from which amino acid?

tyrosine

NE release from sympathetic nerve terminals occurs thru

calcium-dependent exocytosis

3 ways to remove NE

1. Reuptake

   1. via active transport mechanism

2. Diffusion into bloodstream

   1. eventually metabolized

3. Enzymatic inactivation

   1. MAO

   2. MAOI

   3. COMT

monoamine oxidase [MAO]

metabolizes NE that’s been transported back into presynaptic nerve terminal

Monoamine oxidase inhibitors [MAOI]

block catecholamine & serotonin breakdown → increase NT lvls

*used in treatment of depression

Catechol-O-methyltransferase [COMT]

breaks down catecholamines

found in many tissues, esp liver, kidneys, & peripheral tissues

2 types of adrenergic receptors

1. alpha receptors

2. beta receptors

alpha-1 receptors

• coupled to Gq proteins

• activate phospholipase C [PLC]

• → increased IP3 & intracellular calcium

alpha-2 receptors

• coupled to Gi proteins

• inhibit adenyl cyclase → decreases cAMP

beta- 1, 2, 3 receptors

• coupled to Gs proteins

• activate AC → more cAMP

Effect of alpha-1 receptors

• smooth muscle contraction

  • vasoconstriction → increase peripheral resistance & BP

  • increase GI & bladder sphincter contraction

  • contraction of radial muscle of iris → pupil dilation [mydriasis]

Effect of alpha-2 receptors

• inhibits sympathetic activity

  • presynaptic autoreceptors

    • neg. feedback by inhibiting further NE release

  • postsynaptic receptors

    • inhibitory effects

      • decrease CNC sympathetic outflow

      • GI tract relaxation, decrease insulin release in pancreas, decrease lipolysis in adipose tissue

      • increase platelet aggregation

Effect of beta-1 receptors

• cardiac stimulation

  • increases HR, conduction velocity, contractility

  • increase renin release and increased lipolysis

Effect of beta-2 receptors

• smooth muscle relaxation

  • BVs supplying heart & skeletal muscles vasodilate [direct blood to active tissues]

  • bronchodilation in lungs [increase O2 uptake]

  • smooth muscle relaxation in uterus, GI tract, & bladder [suppress nonessential function]

  • increase glycogenolysis, lipolysis, and insulin release [promote glucose uptake]

*more sensitive to EPI than NE

Effect of beta-3 receptors

• metabolic regulation & smooth muscle relaxation

  • increased lipolysis [support sustained E]

  • relaxation of detrusor muscle in bladder [promotes urinary retention during stress]

  • thermogenesis [increase heat production]

Horner Syndrome

• rare disorder affecting eye & nearby tissue on 1 side of face

• caused by interruption of sympathetic pathway to eye

  • most commonly in cervical sympathetic chain [preganglionic fibers]

• symptoms occur on same side [ipsilateral] as lesion

  • Ptosis [drooping of upper eyelid]

    • paralysis of superior tarsal muscle

  • Miosis [constricted pupil]

    • unopposed parasympathetic stim. of sphincter pupillae

  • Anhidrosis [diminished or absent sweating of face]

  • Flushing of face

    • loss of sympathetically mediated vascular tone → vasodilation

Pheochromacytoma

• rare tumor of chromaffin cells of adrenal medulla → excessive catecholamine secretion

• associated with increased excretion of 3-methoxy-4-hydroxymandelic acid [VMA]

• Symptoms

  • increased HR, palpitations, episodic HTN, sweating, tremor, anxiety, headache

• Treatment: Adrenalectomy

which system is dominant at rest?

parasympathetic

postganglionic parasympathetic fibers mainly release

ACh

parasympathetic fibers involved in [SLUDD + M]

Salivation

Lacrimation

Urination

Digestion

Defecation

Miosis

pelvic nerves innervate [S2-S4]

• hindgut derivatives

• urinary bladder & urethra

• reproductive organs

*PPP [poop, pee, penile erection]

ciliary ganglion

CN III

location of postganglionic cell bodies

pterygopalatine ganglion

CN VII

location of postganglionic cell bodies

lacrimal, nasal, & palatal glands → increase secretion

submandibular ganglion

CN VII

location of postganglionic cell bodies

submandibular & sublingual glands → increase saliva

otic ganglion

CN IX

location of postganglionic cell bodies

parotid gland → increase saliva

choline acetyltransferase [ChAT]

catalyzes synthesis of ACh by transferring acetyl group from Acetyl-CoA to choline

Acetylcholinesterase [AChE]

removes ACh by hydrolyzing it into acetate ion & choline

ACh acts on these receptors

nicotinic

muscarinic

nicotinic receptors

• serve as ligand-gated ion channels

• ionotropic receptors [activation directly opens a cation channel]

  • influx of Na+, efflux of K+ → rapid depolarization

2 subclasses of nicotinic receptors

1. Nm [muscle type]

2. Nn [neuronal type]

Curare

• South American arrow poison that acts as a competitive antagonist of Nm nicotinic receptors

• prevents ACh from binding → prevents channel opening → skeletal muscle paralysis

Muscarinic receptors

• metabotropic receptors

  • receptor is separate from ion channel

  • transduces signal indirectly thru intracellular 2nd messenger systems

    • GPCRs

5 muscarinic receptor subtypes

M1, M3, M5 → Gq-coupled

M2, M4 → Gi-coupled

*Gi [esp M2 receptors] open G-protein-gated inwardly rectifying K+ [GIRK] channels to hyperpolarize cell

M1 receptor

CNS, autonomic ganglia, gastric parietal cells

• cognitive function, neurotransmission & gastric acid secretion

M2 receptor

heart, CNS

• open GIRK channels to hyperpolarize cardiac pacemaker cells

  • decrease HR, conduction velocity, and atrial contractility

Atropine

competitive muscarinic receptor antagonist

blocks M2 receptors in heart → increase HR

M3 receptor

smooth muscle, eye, GI tract, bladder, exocrine glands

• increase insulin & exocrine secretions

• increase GI peristalsis

• increase bladder contraction

• bronchoconstriction

• increase pupillary sphincter constriction [miosis]

• vasodilation [endothelial NO release]

M4 receptor

CNS, autonomic ganglia

• motor control, CNS inhibition

M5 receptor

cerebral BVs

• may regulate cerebral blood flow

Neurocardiogenic Syncope / Vasovagal Syncope

• increased parasympathetic activity w/simultaneous withdrawal of sympathetic tone

• triggered by prolonged standing, emotional distress, pain, fear, dehydration, or heat exposure

• prodromal symptoms

  • lightheadedness, nausea, sweating, blurred vision, pallor

• increased vagal tone → M2 receptor activation in heart → bradycardia

• withdrawal of sympathetic tone → peripheral vasodilation

Argyll Robertson Pupil

• associated w/ tertiary neurosyphilis

• light-near dissociation

  • pupil does NOT constrict in response to light

  • but constricts normally during accommodation [focusing on a near object]

    • separate pathways

• damage to pretectal region or its connections interrupts the light reflex pathway

Edinger-Westphal nuclei

pretectal nucleus sends bilateral projections here

these nuclei provide parasympathetic innervation to sphincter pupillae via CN III