Human Physiology: Autonomic Nervous System

Study Guide – Autonomic Nervous System

Structure and Function of the Autonomic Nervous System
anatomic organization of the autonomic nervous system
- general
- two divisions
- cranio-sacral: parasympathetic efferents
- thoraco-lumbar: sympathetic efferents
- organization: ALWAYS two neurons in series
- nucleus: cluster of cells
- ganglion: cluster of cell bodies, and location where synapses may occur
- pre-ganglionic: prior to synapse
- post-ganglionic: after synapse
- characteristics
- mostly peripheral
- effectors
- smooth muscle
- cardiac muscle
- glands
- effector activators
- reflexes
- input from higher centers
- primary functions
- maintain homeostasis (constancy of internal environment)
- function in survival of organism

- parasympathetic (cranio-sacral) pathways
- function: vegetative state (energy conservation)
- organization
- pre-ganglionic cell bodies
- cranial: motor nuclei in the mid-brain and medulla
- sacral: lateral horn of the sacral spinal cord
- pre-ganglionic axons
- cranial: exit brainstem via CN III, VII, IX, and X
- sacral: follow pelvic nerve to intrinsic ganglia in or near organs
- post-ganglionic cell bodies: parasympatetic ganglia in or near organs being innervated
- post-ganglionic axons: continue from ganglia to organs being innervated
- processes: typically unbranching, discreet, targeted to specific organs
- pre-ganglionic: generally small, myelinated, and longer
- post-ganglionic: generally small, unmyelinated, and shorter

- sympathetic (thoraco-lumbar) pathways
- function: fight, flight, or fright
- response is systemic, rather than discreet
- sympathetic activation during standing (blood pressure) can also cause pupil dilation, sweating
- organization
- pre-ganglionic cell bodies: lateral horn of the thoraco-lumbar spinal cord
- pre-ganglionic axons: project from thoraco-lumbar spinal cord
- post-ganglionic cell bodies: paravertebral (chain) ganglia, prevertebral ganglia
- post-ganglionic axons: frequently course with blood vessels
- processes : frequently branching, diffuse, systemically targeted
- pre-ganglionic: generally shorter
- post-ganglionic: generally longer
- ganglia
- paravertebral ganglia: sympathetic chain ganglia, connected to spinal nerve via rami
- appears segmental, and sympathetics can ascend or descend within the chain
- white communicating ramus: contains outgoing preganglionic sympathetics
- gray communicating ramus: contains postganglionic sympathetics that are returning to spinal nerves
- prevertebral ganglia: ganglia associated with other organs
- typically named by location (e.g. inferior, superior mesenteric ganglia)
- synaptic routes
- (1) synapse in chain ganglion, rejoin spinal nerve and continue to target
- (2) synapse in chain ganglion, branch to organ via direct processes
- (3) pass through chain ganglion and synapse in peripheral ganglion, continue to target
- (4) synapse within organ (adrenal glands only)

- innervation of the adrenal medulla
- apparent exception to the two neuron rule, due to synapse location within adrenal medulla
- however, medullary chromaffin cells are homologous to sympathetic postganglionic neurons
- arise from the same neural crest
- released chemical messengers are similar
relationship of function to structure in the autonomic nervous system
- sympathetic nervous system
- function: fight or flight responses
- mobilizes energy reserves
- increases cardiac output
- redirects blood flow to specific organs (muscle, skin)
- organization: diffuse, permitting more systemic response
- outputs: diverging to multiple systems
- inputs: converging to specific target organs
- exceptions: discreet actions
- relaxation of the urinary bladder smooth muscle during storage of urine
- pupillary dilation in response to dim light
- parasympathetic nervous system
- function: homeostasis, discreet elements of the sexual response
- reduced heart rate
- increases intestinal activity
- causes emptying of the urinary bladder
- causes penile erection (yay!)
- causes pupillary constriction
- organization: targeted, with little convergence or divergence
- pre-ganglionic axons rarely branch, even in nerves where several organs are targeted
- as such, parasympathetic nervous system does not discharge systemically

TABLE: Salient Features of the Divisions of the Autonomic Nervous System
parasympathetic sympathetic
outflow from CNS cranio-sacral thoraco-lumbar
location of ganglia in or near the innervated organ paravertebral, prevertebral ganglia
pre-ganglionic axon long, myelinated; unbranched short, myelinated; branched
post-ganglionic axon short, restricted long, diffuse distribution
ganglionic transmitter acetylcholine acetylcholine
transmitter at effector acetylcholine norepinephrine
responses localized (discreet) generalized (diffuse)

dual vs. sole innervation of peripheral organs
- dual innervation
- most autonomic effectors receive innervation from both sympathetic and parasympathetic divisions
- antagonism
- in most organs, effects of sympathetic and parasympathetic system are opposite
- sum of inputs determines action of organ
- typically, input from parasympathetic and sympathetic systems can be deduced from their roles in survival
- summation
- in some organs, effects of sympathetic and parasympathetic system combine
- example: sexual response cycle
- erection: parasympathetic (“point”)
- orgasm: sympathetic (“shoot”)
- single innervation
- some organs are innervated solely by sympathetic neurons
- blood vessels
- piloerector muscles (smooth muscle in hair follicles)
- sweat glands
- catecholamines
- circulating catecholamines generally influence activity of any organ receiving sympathetic input
- it is catecholamines, not direct innervation of sweat glands, that causes emotional sweating

TABLE: Effects of Sympathetic and Parasympathetic Activity
organ effects of sympathetic stimulation effects of parasympathetic stimulation
heart
muscle

conducting tissue
↑ rate
↑ force of contraction (A, V)
↑ AP conduction velocity
↓ rate
↓ force of contraction (A only)
↓ AP conduction velocity
blood vessels
most vessels
coronary arteries
skeletal muscle
constriction
dilation
constriction (typically)
--- (except genital vasoconstriction)
---
---
digestive tract
smooth muscle
glands
↓ motility
↓ secretion
↑ motility
↑ secretion
lungs
airways
glands
dilation of bronchioles
inhibition of mucus secretion
constriction
stimulate secretion
eye (iris) dilation of pupil constriction of pupil
exocrine glands
sweat glands
salivary glands
↑ sweating
small volume, thick saliva
---
large volume, watery saliva
adrenal medulla ↑ secretion
(norepinephrine, epinephrine) ---
genitals orgasmic contractions (“shoot”) erection (“point”)

autonomic reflexes
- autonomic nervous system outflow tracts are the efferent limbs of reflex arcs
- activity depends on afferent sensory pathways, control from higher centers (esp. brainstem)
- somatic afferents may form excitatory synapses on preganglionic cell bodies
- somatic afferents may synapse on interneurons that excite or inhibit preganglionic cells
- thus somatic, autonomic nervous systems influence one another via reflex pathways
- differences between somatic, autonomic reflexes
- conduction velocity
- autonomic: slow
- somatic: fast
- inhibition
- autonomic: multiple sites of inhibition in autonomic effector organs (i.e. central or neuro-effector synapse)
- somatic: inhibition only possible in central nervous system




Autonomic Pharmacology and Pathophysiology
preganglionic neurotransmitters
- common transmitters
- excitatory: glutamate, aspartate
- inhibitory: glycine, γ-amino butyric acid (GABA)
- other neurotransmitters or modulators
- serotonin: excitatory at preganglionic neurons projecting to the urinary bladder
inhibitory at preganglionic neurons projecting to the cardiovascular system
- peptides: can influence excitability or preganglionic neurons
ganglionic neurotransmitters
- transmitter: acetylcholine (ACh)
- function: neurotransmitter at ganglionic synapses in both sympathetic, parasympathetic systems
- mechanism: binds post-synaptic receptors, resulting in a post-ganglionic EPSP
- increases probability of reaching threshold for an action potential
- increases likelihood of transmitter release by the post-ganglionic neuron
- receptors: nicotinic, muscarinic
- nicotinic (N) receptor
- type: excitatory
- mechanism: EPSP via ↑gK, gNa (giving net depolarization)
- agonist: nicotine
- blocker: TEA, hexamethonium
- muscarinic (M1) receptor
- type: excitatory
- mechanism: ↑gCa, ↓gK (via PKC protein phosphorylations)
PLC activity: cleaves PIP2 into IP3, DAG
- IP3: increased [Ca2+]
- DAG: activation of PKC
- agonist: muscarine: toxin produced by certain mushrooms
transmitters at neuro-effector junctions
- neurotransmitters
- ganglionic synapse
- parasympathetic: acetylcholine
- sympathetic: acetylcholine
- neuro-effector junction
- parasympathetic: acetylcholine
- sympathetic: norepinephrine, epinephrine (adrenal medulla only)

- parasympathetic receptors
- M2 receptor
- location: cardiac atrial muscle, conducting tissue of the SA and AV node
- effect: depressive effects on atrial function
- decreased atrial contractility
- decreased conduction velocity of atrial action potentials
- decreased heart rate
- mechanism: inhibition of adenylate cyclase: anti-β effects
↑gK: decreased heart rate
- M3 receptor
- location: visceral smooth muscle, secretory glands
- effect: increased smooth muscle contraction, glandular secretions (↓gK)
- mechanism: membrane depolarization: due to PKC-induced ↓gK
- sympathetic receptors
- α1 adrenergic receptor
- agnoists: norepinephrine > epinephrine > isoproterenol
- blocker: prasozin
- location: vascular smooth muscle, urogenital smooth muscle, gut smooth muscle
- effect: excites vascular smooth muscle (↑gNa, ↓gK)
inhibits gut smooth muscle (Ca2+-dependent ↑ gK)
- mechanism: activates phospholipase C (↑ PKC via diacylglycerol)
- α2 adrenergic receptor
- agonists: norepinephrine > epinephrine > isoproterenol
- location: sympathetic post-ganglionic axon terminals
- effect: decreased neurotransmitter release
- mechanism: ↓gCa
- β1 adrenergic receptor
- agonists: isoproterenol > epinephrine > norepinephrine
- blockers: propranolol, attenolol
- location: heart muscle, nodal tissue
- effect: increased effects on heart function
- increased atrial contractility
- increased conduction velocity of atrial action potentials
- increased heart rate (↓gK)
- mechanism: activates adenylate cyclase (↑ PKA, channel phosphorylations)
- β2 adrenergic receptor
- agonists: isoproterenol > epinephrine > norepinephrine
- location: bronchial smooth muscle, GI smooth muscle, some skeletal muscle vasculature
- effect: muscular relaxation
- mechanism: hyperpolarization (PKA-dependent activation of Ca2+-dependent gK increase)
- β3 adrenergic receptor
- agonists: isoproterenol > epinephrine > norepinephrine
- location: adipose tissue
- effect: lipolysis
- mechanism: activates adenylate cyclase

TABLE: Transmitters and Receptors of the Autonomic Nervous System
synapse transmitter receptor effector post-synaptic effect mechanism
ganglionic synapses ACh mostly N
some M1 (post-synaptic cell) depolarization
depolarization ↑gNa, ↑gK
PKC-induced ↑gCa, ↓gK
parasympathetic neuro-effector junction ACh M2 atrial muscle
cardiac nodal tissue ↓ contractility
↓ AP conduction velocity
↓ heart rate anti-β effects (↓ PKA via inhibition of adenylate cyclase); ↑gK
ACh M3 visceral smooth muscle
secretory glands
↑ contraction
↑ secretion PKC-induced ↓gK
sympathetic neuro-effector junction norepinephrine α1 vascular smooth muscle
urogenital smooth muscle ↑ contraction PKC-induced ↑gCa, ↓gK
norepinephrine α2 sympathetic post-ganglionic
axon terminals ↑ transmitter release ↓gCa
norepinephrine β1 heart muscle
nodal tissue ↑ contractility
↑ AP conduction velocity
↑ heart rate PKA-induced ion channel, contractile protein phosph.
norepinephrine β2 bronchial smooth muscle
GI smooth muscle relaxation PKA activation of Ca2+-dependent gK
norepinephrine β3 adipose cells lipolysis ↑ adenylate cyclase activity

- summary
- ganglionic
- nicotinic: excitatory: depolarizing increase in excitability (↑gK, gNa)
- muscarinic: excitatory: PKC-induced ↑gCa, ↓gK
- neuro-effector
- M2: cardiac (atrial) depressor: anti-β effects (↓ PKA) on contraction and velocity, ↑gK on rate
- M3: visceral, glandular contraction: PKC-induced ↓gK (depolarization)
- α1: vascular, urogenital contraction: PKC-induced ↑gCa, ↓gK (depolarization)
- β1: cardiac pressor: PKA-induced phosphorylations (contractile, channel proteins)
- β2: bronchial, gut relaxation: PKA-induced hyperpolarization (Ca2+-dependent gK)

- generalizations
- β receptors: effects on PKA
- muscarinic neuro-effectors: do not have effects on gCa
- α1, M1: same effects on ion channels


skeletal muscle vascular beds
- mediating blood pressure: vasoconstriction of smooth muscle in skeletal muscle vasculature
- innervation: adrenergic sympathetic post-ganglionic neurons
- receptors: α1 adrenergic receptors
- location: not found in heart or brain
- effect: generalized vasoconstriction and increased blood pressure
- logic: increases peripheral resistance to blood flow, diverting to heart and brain
- overriding vasoconstriction: exercise
- anticipation of exercise causes generalized sympathetic discharge and vasoconstriction
- exercise requires increased blood flow to peripheral tissues
- during exercise, CO2 and H+ are generated, overriding the sympathetic signal and causing vasodilation
- note: some people have β2 receptors in peripheral vasculature, which can allow anticipatory vasodilation
secretions of the adrenal medulla
- adrenal medulla
- innervation: preganglionic: sympathetic neuron
postganglionic: chromaffin cells
- function: release of catecholamines (80% epinephrine, 20% norepinephrine)
- catecholamines:
- effect: agonists for both α, β receptors
- half life: short (~ 20 seconds), due to rapid uptake and breakdown in tissues
disorders of the autonomic nervous system (do not memorize)
- idiopathic orthostatic hypotension
- symptoms: acute fall in blood pressure when an individual stands or walks
- etiology: cell loss in sympathetic and vagal efferent pathways (loss of vasoconstriction)
- acute autonomic neuropathy
- symptoms: blurred vision, loss of sweating, constipation, retention of urine, dry mouth, impotence
- etiology: degeneration of parasympathetic (and sometimes sympathetic) pre-ganglionic neurons
- pheochromocytoma
- symptoms: hypertension, headache, high heart rate, sweating
- etiology: excessive production of catecholamines, often secondary to cancer of chromaffin cells
- botulism
- symptoms: weakness/paralysis, blurred vision, urine retention, dry mouth, dysphagia, postural hypertension
Horner symptoms: fixed, dilated pupils (miosis), drooping of the eyelids (ptosis)
- etiology: toxin-inhibited Ca2+-dependent release of ACh at axon terminals
- source: Clostridium botulinum
- tetanus
- symptoms: muscular rigidity, hypertension, tachycardia, sweating
- etiology: toxin-induced block of release of inhibitory neurotransmitters (glycine, GABA) from interneurons
effect is to release α-motor neurons from inhibitory control
- source: Clostridium tetani