Module 2 - The Autonomic Nervous System

2/4/26 and 2/6/26 lectures

autonomic nervous system (ANS)

part of the central nervous system

composed of the sympathetic and parasympathetic systems

has afferent and efferent pathways

functions mostly at the subconscious level (autonomic = automatic, not within our conscious control)

functions of the ANS

controls functions of many organs and tissues in the body

innervates visceral organs, glands (e.g. sweat glands), blood vessels (walls of blood vessels → controls blood pressure)

regulates visceral organs

efferent fibers of the ANS

cell bodies are in the spinal cord and reach sympathetic ganglia

(sympathetic ganglia are located on both sides of the vertebral column)

parasympathetic efferents reach ganglia at/near organs

organization of the ANS

preganglionic neuron cell bodies are in the CNS

preganglionic neurons’ bodies originate the CNS

in autonomic neuroganglia: preganglionic neurons form a synapse with the bodies of postganglionic neurons

postganglionic neurons synapse on effector organs

the adrenal medulla is an example of a specialized ganglion of the sympathetic NS

adrenal medulla

a specialized ganglion of the sympathetic NS

preganglionic fibers synapse on chromaffin cells

chromaffin cells secrete epinephrine and norepinephrine (80% epi and 20% norepi) into circulation

clinical point: pheochromocytoma

adrenal medulla can form a tumor that secretes excessive catecholamines and increase excretion of VMA (3-methoxy-4-hydroxymandelic acid)

sympathetic nervous system

“fight-or-flight” system (e.g. during exercise, fear)

prepares and mobilizes body in emergency cases

stimulation leads to: increased HR, constriction of arterioles of skin and intestine, dilation of arterioles in skeletal muscle, raised BP, dilation of pupils, closing of sphincters, raising of hair, sweating

parasympathetic nervous system

“rest and digest” system

conserves and stores energy when body is relaxed (e.g. during sleep)

stimulation leads to: decreased HR, pupil constriction, increased peristalsis (increased GI motility), increased glandular activity, opening of sphincters, contraction of bladder wall

(parasympathetic is the parachute to slow down your body’s fight-or-flight)

efferent origin of the ANS

spinal cord, broadly

sympathetic NS originates from thoraco-lumbar region (cell bodies in the lateral horn of T1-L2/3) (red in picture)

parasympathetic NS originates from cranio-sacral region (CN III, CN VII, CN IX, CN X, S2-4) (black in picture)

pathway of efferent sympathetic outflow

pre-ganglionic fibers originate from spinal cord → travel to sympathetic ganglion (parallel to spinal cord) → have synapse with post-sympathetic ganglion → releases neurotransmitter (ACh) → ACh stimulates post-ganglionic fiber → post-ganglionic fiber releases epinephrine → post-ganglionic fiber travels to internal organs and releases norepinephrine (norepinephrine binds to receptors on heart, etc)

in picture, circles are sympathetic ganglia (follow the red pathway)

adrenergic receptors

receptors in the sympathetic NS

receive norepinephrine

alpha receptors a-1 and a-2

beta receptors b-1 and b-2

dopamine receptors D1 and D2

effect depends on type of receptor and location on cell

cholinergic receptors

receptors in the parasympathetic NS (and sympathetic?)

receive ACh

peptidergic receptors

receptors in the parasympathetic NS

receive peptides, e.g. substance P, vasoactive inhibitory peptide

alpha-1 receptors

an adrenergic receptor

located on vascular smooth muscle of skin and splanchnic regions, GI and bladder sphincters, and radial muscle of iris

produce excitation (contraction)

equally sensitive to norepinephrine and epinephrine

^but only norepinephrine is released enough from adrenergic neurons to activate a-1 receptors

mechanism of action of an alpha-1 receptor

G-protein alpha stimulator → phospholipase C → inositol formation → IP3 → increase intracellular Ca²⁺ (because Ca²⁺ is needed for muscle contraction)

clinical point about norepinephrine

physiological effect of norepinephrine: muscle contraction and vasoconstriction

excessive release of norepinephrine or excess absorption → hypertension (side symptoms: headache, vertigo, nosebleeds, sleep disorder, excess sweating, heart palpitations)

treated with an alpha-1 receptor blocker, e.g. Prazosin

alpha-2 receptors

an adrenergic receptor

located in presynaptic nerve terminals, platelets, fat cells, walls of GI trat

often produce inhibition (relaxation, dilation)

receives only neuroepinephrine

mechanism of action of an alpha-2 receptor

G-protein alpha inhibitor → inhibition of adenylate cyclase → decrease in cAMP

beta-1 receptors

an adrenergic receptor

located in SA node, AV node, and ventricular muscle (myocardium) of heart

produces excitation (increased HR, increased conduction velocity, increased contractility)

sensitive to both norepinephrine and epinephrine

more sensitive than alpha-1 receptors

mechanism of action of a beta-1 receptor

activation of G-protein alpha-stimulator → activation of adenylate cyclase → increase in cAMP

(same as beta-2 mechanism)

clinical point: excess norepinephrine on the heart

increased heart rate

palpitations, tachycardia, arrhythmia

treated with beta-1 blockers, e.g. propranolol

beta-2 receptors

an adrenergic receptor

located on vascular smooth muscle of muscle, bronchial smooth muscle, in walls of GI tract and bladder, liver, pancreatic beta-cells

produces relaxation (dilation of vascular smooth muscle and bronchioles, relaxation of bladder wall)

more sensitive to epinephrine than norepinephrine

more sensitive to epinephrine than alpha-1 receptors

mechanism of action of a beta-2 receptor

activation of G-protein alpha-stimulator → activation of adenylate cyclase → increase in cAMP

(same as beta-1 mechanism)

clinical point about beta-2 receptors

asthmatic patients should be given beta-2 agonists, e.g. albuterol, to relax smooth muscle of bronchi

asthmatics with heart palpitations cannot be given propranolol + albuterol because propranolol blocks beta-1 and recognizes beta-2, but beta-2 doesn’t want to be blocked (would aggravate asthma)

atenolol + albuterol is better for asthmatics

key points about beta blockers and agonists

Propranolol is Beta blocker 1 and 2

Albuterol is beta 2 agonist

Atenolol is Beta 1 blocker (not Beta 2)

nicotinic receptors

a cholinergic receptor

located in autonomic ganglia of sympathetic and parasympathetic NS, at neuromuscular junction, and in adrenal medulla

^receptors are similar, not identical

activated by ACh or nicotine

produce excitation

blocked by ganglionic blockers in autonomic ganglia, but not at neuromuscular junction

mechanism of action for nicotinic receptors

ACh binds to alpha subunits of receptor

receptors also serve as ion channels for Na+ and K+

muscarinic receptors

a cholinergic receptor

located in heart, smooth muscle, and glands

inhibitory in heart

excitatory in smooth muscle and glands (decreased HR

activated by ACh and muscarine

blocked by atropine

mechanism of action of

brain stem

made of the medulla oblongata, pons, and midbrain

a collection of autonomic centers

medulla as an autonomic center

vasomotor center

respiratory center

swallowing, coughing, and vomiting centers

pons as an autonomic center

pneumotaxic center (part of the autonomic respiratory centers)

midbrain as an autonomic center

micturition center (part of the renal system)

hypothalamus as an autonomic center

temperature regulation center

thirst and food intake regulatory centers

difference in neurotransmitters of the ANS

preganglionic: ACh

postganglionic: ACh in parasympathetic, norepinephrine in sympathetic

when there is excess ACh secretion from vagus nerve in parasympathetic, what is side effect in heart?

bradycardia, decreased contractility, decreased conduction velocity

sympathetic NS effects on the eye

alpha-2 receptors dilate pupils

beta-receptors accommodate the ciliary muscle

decreased secretion in lacrimal gland

parasympathetic NS effect on eye

salivary glands

parasympathetic salivary glands

sympathetic on heart

parasympathetic on heart

chronotropic

heart rate

dromotropic

conductivity

sympathetic lungs

parasympathetic lungs

clinical case: excess ACh, what is the side effect on heart?

bradycardia

clinical case: xs ACh, side effect on GI tract?

increased peristalsis → diarrhea?

xs ACh → side effect on stomach?

increased HCl secretion for digestion → gastritis

clinical case: oversecretion of norepinephrine → side effect on heart?

tachycardia, arrhythmia, palpitations

clinical case: pt has constipation, erectile dysfunction, palpitations, hypertension

excess norepinephrine production, not enough ACh