Chapter 60
Sunday, December 02, 2012
4:11 PM
Autonomic Nervous System and the Adrenal Medulla

ANS - controls most visceral functions of the body; changes can occur w/rapidity and intensity
 Activated mainly by centers located in SC, brain stem, and hypothalmus
 Portions of cerebral cortex (esp limbic cortex) can transmit signals to lower centers and influence autonomic
control
 Often operates thru visceral reflexes
o Subconscious sensory signals from a visceral organ enters autonomic ganglia/brain stem/hypothalmus
and returns subconscious reflex responses directly back to the visceral organ to control its activities
o Efferent autonomic signals transmitted to organs via SNS and PSNS
 SNS
o Peripheral Portions
 Two paravertebral sympathetic chains of ganglias interconnected w/spinal nerves on side of
vertebral column
 Two prevertebral ganglia (celiac and hypogastric)
 Nerves extending from ganglia to different organs
o Sym nerve fibers originate in SC w/spinal nerves b/w T1 -L2 and pass into sympathetic chain then to
tissues and organs
o Preganglionic Neurons
 Cell body in intermediolateral horn of SC -> anterior root -> spinal nerve -> white ramus -> ganglia
of sympathetic chain then:
1. Synapse w/postganglionic sym neurons in ganglion
2. Pass up/down in chain and synapse in other ganglia in chain
3. Pass for variable distances thru chain, thru sym nerve -> synapsing in a peripheral sym
ganglion
o Postganglionic Neurons
 Originates in one of the sym chain ganglia or in one of peripheral sym ganglia
 Some pass back from sym chain into spinal nerves thru gray rami (all very small type C fibers);
extend to all parts of the body by way of skeletal nerves
 Control blood vessels, sweat glands, and piloerector muscle
 ~8% of fibers in avg skeletal nerves are sym fibers
o Sym fibers termination - determined partly by locus in embryo
 T1 - terminate in head
 T2 - neck
 T3-T6 - thorax
 T7-T11 - abdomen
 T12, L1-L2 - legs
o Adrenal Medullae
 Preganglionic sym nerve fibers pass W/O SYNAPSING, from intermediolateral horn cells of SC ->
sym chains -> splanchnic nerves -> into adrenal medullae
 End directly on modified neuronal cells that secrete epinephrine and norepinephrine into the
blood
 Modified neuronal cells - derived from nervous tissue and are postganglionic neurons
 PSNS
o Parasym fibers leave CNS thru cranial nerves III, VII, IX and X and 2nd and 3rd sacral spinal nerves
(occasionally thru 1st and 4th sacral spinal nerves)
o 75% of all parasym fibers are in vagus nerves (entire thoracic and abd regions)
 CN III: pupillary sphincter and ciliary muscle of eye
 CN VII: lacrimal, nasal, and submandibular glands
 CN IX: parotid gland



CN X: heart, lungs, esophagus, stomach, SI, CO-prox, liver, GB, pancreas, kidneys, upper ureters
Sacral parasym fiber are in pelvic nerves (sacral plexus S2-S3)
 COD, rectum, urinary bladder, lower ureters, external genitalia - erection
o Preganglionic fibers pass uninterrupted all the way to the target organ; postganglionic neurons are
located in the wall of the organ
 Extremely short postganglionic fibers leave neurons to innervate the organ tissues
 Few exceptions
Sym/Parasym Function
o Two synaptic transmitter substances
 Acetylcholine
 Secreting fibers - cholinergic
 All preganglionic neuron in both SNS/PSNS
 All (or almost all) postganglionic neurons of PSNS
 Postganglionic sym nerve fibers to sweat glands, piloerector muscles, very few blood
vessel
 "Parasympathetic Transmitter" but will excite both sym/parasym postganglionic neurons
 Synthesized in terminal endings/varicosities of cholinergic nerve fibers - stored in vesicles
(highly concentrated form)
 Persists in tissues for a few secs, then is split (see biochem pathway)
 Norepinephrine
 Secreting fibers - adrenergic
 Most of postganglionic sym neurons (few secrete acetylcholine)
 "Sympathetic Transmitter"
 Synthesis begins in axoplasm of terminal nerve endings of adrenergic nerve fibers;
completed inside the secretory vesicles
 Removed from secretory site by:
 Reuptake into adrenergic nerve endings by active transport (50-80% of removal)
 Diffusion away from nerve endings into surrounding body fluids then into blood
 Destruction of small amounts by tissue enzymes
 Secreted directly: remains active for only a few secs (reuptake/diffusion away is rapid
 Secreted into blood: remain active until diffuses into tissue (mainly liver), remains active for
10-30 secs, activity declines to extinction over 1-several minutes
o Secretion
 Many PSNS fibers/almost all SNS fibers merely touch effector cells of target organs
 Some terminate in connective tissue located adjacent to target cells
 Have bulbous enlargements called varicosities
 acetylcholine or norepinephrine are synthesized and stored
 Has large #'s of mitochondria supply ATP
 AP spreads over terminal fibers -> depolarization process inc permeability of fiber membrane to
Ca+ -> ions diffuse into nerve terminals or nerve varicosities -> ions cause them to empty contents
to exterior - transmitter substance is secreted
o Receptors on Effector Organs
 Must bind w/specific receptors on effector cells
 Receptor - bound as a prosthetic group to a protein molecule - goes thru membrane all the way
 Binding causes conformational change
 Altered protein molecule excites/inhibits the cell
 Causing change in cell membrane permeability to one or more ions
 Often opens/closes an ion channel
 i.e. Na+ and/or Ca+ ion channels freq are opened -> allow rapid influx of ions into cell
 Usually depolarizing cell membrane and exciting the cell
 i.e. K+ channels are opened allowing K+ to diffuse out of cell -> inhibits cell b/c loss of
electropositive K+ ions creates hypernegativity inside the cell
 Activating/inactivating an enzyme attached to the other end of the receptor protein


o
o
o
o
Enzyme often attached to receptor protein where receptor protrudes interiorly
i.e. binding of norepinephrine w/receptor inc the activity of enzyme adenylyl cyclase
inside the cell -> causes formation of cAMP -> initiates action
 Acetylcholine Receptors
 Muscarinic - Muscarine (toadstool poison) only activates muscarinic receptors
 Found on all effector cells stim by postganglionic cholinergic neurons of SNS/PSNS
 Nicotinic - Nicotine only activates nicotinic receptors
 Found in autonomic ganglia at synapses b/w pre/postganglionic neurons of SNS/PSNS
 Adrenergic Receptors
 Alpha (both excitatory/inhibitory)
 Alpha1, alpha2
 Norepinephrine - excites mainly
 Epinephrine - excites
 Isopropyl norepinephrine - no action
 Beta (both excitatory/inhibitory)
 Beta1, beta2, beta3
 Norepinephrine - excites to a lesser extent
 Epinephrine - excites
 Isopropyl norepinephrine - strong action
Function of Adrenal Medullae
 Stimulation of sym nerves -> large quantities of epinephrine/norepinephrine to be released in
blood
 80% epinephrine, 20% norepinephrine
 Effects last 5-10X longer than direct sym stim, b/c hormone are removed slowly (2-4 min)
 Circulating norepinephrine -> constriction of most vessels, inc heart activity, inhibition of GI
tract, dilation of pupils, inc total peripheral resistance and elevates arterial pressure
 Circulating Epinephrine -> same effects, plus: greater heart stim b/c better effect in stim
beta receptors, weaker constriction of blood vessels, raises arterial pressure to lesser
extent, inc cardiac output more, 5-10X metabolic effect (can inc metabolic rate of body as
much as 100% above normal - inc activity/excitability of body)
 Stim of Target Organs
 Organs stim directly by SNS and indirectly by adrenal medullary hormones simultaneously
 Two systems support and can substitute each other (provides a safety net for
stimulation)
 Normal resting rate of secretion ~ 0.2 ug/kg/min of epinephrine; 0.05 ug/kg/min of
norepinephrine
 Quantities are enough to maintain the BP almost to normal even if all direct sym pathways
to cardiovascular system are removed
Stimulus Rate
 ANS - lower freq of stim required for full activation (compared to skeletal NS)
 Only one nerve imulse/few secs to maintain normal SNS/PSNS effect
 Full activation occurs when fibers discharge 10-20 times/sec
 Skeletal NS at 50-500+ impulses/sec
Sym/Parasym Tone
 Value of tone = allows a single NS both to inc and dec the activity of a stimulated organ
 i.e. Sym tone: systemic arterioles constricted to ~ 1/2 their max diameter
 This way the SNS can both cause vasoconstriction and vasodilation
 i.e. Surgical removal of parasym supply to GI by cutting vagus nerves -> serious/prolonged GI
atony -> blockage of normal GI propulsion -> serious constipation :(
Denervation
 Sym/Parasym nerve cut -> innervated organ loses its sym/parasym tone
 Intrinsic tone - occurs over min/hours/days/weeks
 After denervation intrinsic tone inc

o
o
o
o
o
i.e. blood vessels - inc tone caused by inc smooth muscle contractile force that is NOT
resultant of sym stim but of chemical adaptations in smooth muscle fibers ->
eventually restores almost normal vasoconstriction
 Intrinsic compensation - return function of the organ almost to its normal basal level
 In PSNS may take many months
 i.e. loss of parasym tone to the heart after cardiac vagotomy inc HR to 160 beats/min
-> still partially elevated 6 months later
 Denervation Supersensitivity - post-denervation, organ is more sensitive to injected
norepinephrine or acetylcholine
 Process:
 Stellate ganglion removed
 Blood flow rises b/c lost vascular tone
 Days/weeks later - blood flow returns toward normal b/c inc in intrinsic tone of
vascular musclature
 Norepinephrine injected, and blood flow dec much more (as compared to before the
denervation) b/c vessels have become ~ 2-4X more responsive to norepinephrine
 Mechanism
 # of receptors in postsynaptic membranes of effector cell inc when
norepinephrine/acetylcholine is no longer released at the synapses
Mass Discharge - almost all portions of the SNS discharge simultaneously as a complete unit
 Freq occurs when hypothalmus is activated by fright, fear, or severe pain
 Alarm or Stress Response - widespread rxn thruout the body (fight or flight response)
 Inc arterial pressure
 Inc blood flow to active muscles, dec flow to organs
 Inc rates of cellular metabolism thruout body
 Inc blood glucose concentration
 Inc glycolysis in liver and in muscle
 Inc muscle strength
 Inc mental activity
 Inc rate of blood coagulation
 Process: hypothalmus stim -> signals transmitted downward thru the reticular formation of
the brain stem and into the SC -> massive sym discharge
SNS Localized Responses
 Process of heat regulation
 SNS controls sweating and blood flow in skin w/o affected other organs
 Local reflexes involving sensory afferent fibers
 i.e. heating a skin area
 GI control functions by way of nerve pathways that do not enter SC
PSNS Localized Responses
 Cardiovascular reflexes usually only act on the heart - change HR
 Isolated parts of the GI system (mouth glands, stomach gland etc)
Medullary, Pontine, and Mesencephalic Control
 Transection of brain stem above midpontine level
 Allows basal control of arterial pressure
 Prevents arterial pressure modulation by higher nervous centers (i.e. hypothalmus)
 Transection immediately below medulla
 Arterial pressure falls to less than 1/2 normal
Control of Brain Stem Autonomic Centers
 Hypothalmus and Cerebrum (higher brain centers)
 i.e. posterior hypothalmus - can activate medullary cardiovascular control centers (inc
arterial pressure to more than 2X normal)
 Autonomic centers in brain stem act as relay stations for control activities initiated at higher levels
of the brain


Higher areas of the brain can alter function of the whole ANS or portions of it strongly enough to
cause severe autonomic-induced dz (i.e. peptic ulcer of STM or SBDU, constipation, heart
palpitation or MI)
Pharmocology of ANS
o Sympathomimetic or Adrenergic Drug
 i.e. Norepinephrine, Epinephrine, Methoxamine
 Norepinephrine/epinephrine have actions 1 to 2 minutes
 Other commonly used sympathomimetic drugs last for 30min to 2 hours
 Phenylephrine - alpha receptors
 Isoproterenol - beta receptors
 Albuterol - only beta2 receptors
o Indirect Sympathomimetic Action
 i.e. ephedrine, tyramine, amphetamine
 Cause release of norepinephrine from its storage vesicles in the sym nerve endings
o Drugs that block Adrenergic activity
 Reserpine
 Synthesis and storage of norepinephrine is sym nerve endings is prevented
 Guanethidine
 Release of norepinephrine from sym endings is blocked
 Phenoxybenzamine and Phentolamine
 Sym alpha receptors are blocked
 Propranolol
 Blocks beta1 and beta2 receptors
 Metoprolol
 Blocks beta1 receptors
 Hexamethonium
 Blocks transmission of nerve impulses thru autonomic ganglia (sym and parasym)
o Drugs that act on Cholinergic Effector Organs
 Cholinergic Drugs (parasym drugs)
 Are not rapidly destroyed like IV acetylcholine
 Produce typical widespread parasym effects
 Commonly used: pilocarpine and methacholin - act directly on muscarinic cholinergic
receptors
 Anticholinesterase Drugs
 Do not have direct effect on parasym effector organs
 Potentiate effect so fnaturally secreted acetylcholine at parasym endings
 Include: neostigmine, pyridostigmine, and ambenonium
 Inhibit acetylcholinesterase, preventing rapid destruction of the acetylcholine
 Quantity of acetylcholine inc w/successive stimuli and the degree of action also inc
 Antimuscarinic Drugs
 Block the action of acetylcholine on the muscarinic cholinergic effector organs
 Do not affect the nicotinic action
 i.e. atropine, homatropine, and scopolamine
o Drugs that stim Autonomic Postganglionic Neurons
 Preganglionic neurons (sym/parasym) secrete acetylcholine at endings -> stim the postganglionic
neurons
 Injected acetylcholine can also stim postganglionic neurons of both systems
 Nicotine  can stim postganglionic neurons b/c nicotinic type of acetylcholine receptor
 Excites both sym and parasym postganglionic neurons at the same time
 Strong sym vasoconstriction in abd organs and limbs
 Parasym effects - inc GI activity and slowing of heart
 Nicotinic Drugs - cause autonomic effects by stim postganglionic neurons


o
Methacholin - both nicotinic and muscarinic actions
Pilocarpine - only muscarinic actions
Ganglionic Blocking Drugs
 Block impulse transmission from the autonomic preganglionic neurons to the postganglionic
neurons
 i.e. tetraethyl ammonium ion, hexamethonium ion, and pentolinium
 Block acetylcholine stim of the postganglionic neurons - both sym and parasym simultaneously
 Seldom used for blocking parasym activity b/c it's sym blocking abilities outshine it's parasym
skills
 Esp can reduce the arterial pressure in pts w/hypertension
 No useful clinically b/c effects are difficult to control