Autonomic Nervous System- involuntary

- 2 Parts : Sympathetic & Parasympathetic NS

SYMPATHETIC NERVOUS SYSTEM

 Ganglia- collection of nerve bodies (Prevertebral Ganglia)

☆ Ganglia is subdivided into:

- Celiac (ganglion) – nerve bodies of neurons that will provide Sympathetic innervation to the
liver, stomach, & pancreas
- Superior Mesenteric – provide Sympathetic neurons that goes into the intestines & iliocecal
valve
- Aorticorenal – goes to the renal medulla and the kidney
- Inferior Mesenteric – to the colon, anal sphincters, ureters & some to the bladder
- Hypogastric plexus- goes to the genitalia, reproductive organs & to the bladder

Sympathetic Spinal Chain –

GANGLIA – Contain the cell bodies of Sympathetic neurons.

- Provide Sympathetic innervation to different organs

Nerves Extending from Ganglia- they will extend to the organs that they will innervate.

Sympathetic Nerve Fibers – originate in the spinal cord along with the spinal nerves between the
segments T1 & L2

○ first goes through Sympathetic chain -> Ganglion -> to the organs

PREGANGLIONIC & POSTGANGLIONIC SYMPATHETIC NEURONS

Each sympathetic pathway has 2 Types of Neurons:

o Preganglionic- neurons before the ganglion; cell bodies will lie in the intermediolateral horn of
the spinal cord. Its fibers will pass through the Ventral Root
o Postganglionic –neurons after the ganglion; cell bodies are found in the ganglion

Ventral Root – goes outward (motor)

Dorsal root – goes inward (sensory)

♧ After the spinal nerve leave the spinal canal -> Preganglionic Fibers will leave spinal nerve -> white
ramus -> Ganglia of sympathetic chain

♧ Preganglionic Fibers – can take one of the ff. Courses: either they

- Synapse IMMEDIATELY with Postganglionic sympathetic neuron in the ganglion that they enter
- Can enter ganglia but go down into another ganglia and synapse there (not immediately)
- Go out into a peripheral ganglion & synapse there

Postganglionic Neuron- originate either in the sympathetic chain ganglia or in the peripheral ganglia.
 - Will then go to the effector cell

SYMPATHETIC NERVE FIBERS IN THE SKELETAL NERVES

 Type C Fibers- go back to the spinal nerves through the gray rami at the level of the cord. Very
small.
- They extend to all parts of the body via skeletal nerves.
- Control blood vessels, sweat glands, piloerrector muscles
- 8% importance

SEGMENTAL DISTRIBUTION OF SYMPATHETIC NERVE FIBERS

◇ Sympathetic pathway are note necessarily distributed to the same part of the body as the somatic
spinal nerve. Will terminate: (approximation)

 T1 – head
 T2 – neck
 T3-6 – thorax
 T7-11 – abdomen
 T12, L1-2 – legs

◇ Distribution is determined partly because of EMBRYONAL ORIGINS.

SPECIAL SYMPATHETIC NERVE ENDINGS IN THE ADRENAL MEDULLAE

♡ intermediolateral horn -> Preganglionic Fiber -> Sympathetic chain-> splanchnic nerves -> adrenal
medulla

♤ Adrenal Medulla- contains Postganglionic Neuron. Modify neuronal cells are found here and they
secrete norepi & epi into the blood stream

- CATECHOLAMINES:
 Epinephrine
 Norepinephrine

♧ Neuronal cells found in adrenal medulla are derived from the nervous system during embryonic
stage/ fetal development. And are modified Postganglionic Neuron and their nerve endings secrete epi
&norepi.

PARASYMPATHETIC NERVOUS SYSTEM

□ simpler than the sympathetic

□ Parasympathetic fibers that leaves from CNS through:

 CN III, VII, IX, X

 S2, S3
 S1, S4
□ vagus (X)- goes through the heart, lungs, esophagus, stomach, entire small intestine, proximal half of
the colon, liver, gallbladder, pancreas, kidneys, & upper portions of the ureters.

- 75% of all Parasympathetic nerve fibers are here

□ occulomotor (III)- pupillary sphincter, & ciliary muscle of the eye.

- responsible for pupillary constriction & focusing of the lens

□ facial (VII)- the lacrimal, nasal, & submandibular glands

- function is both sensory & motor

□ glassopharyngeal (IX)- parotid gland

□ S2, S3 – descending colon, rectum, urinary bladder, & lower portions of ureters.

- Parasympathetic fibers are in the pelvic nerves which will pass through the spinal nerve, sacral plexus
on each side of the cord @ S2 & 3.

-in males: Parasympathetic NS- causes erection; Sympathetic NS causes ejaculation.

PREGANGLIONIC & POSTGANGLIONI PARASYMPATHETIC NEURONS

☆ in some cases the Preganglionic Fibers will pass uninterrupted all the way to the organ they will
control. In the organ there will be Postganglionic Neuron that are located in the walls.

*Difference: Parasympathetic- from the brain/spinal cord will go out into the organs directly w/o
synapsing; they will synapse with Postganglionic neuron in the wall of the organs. Sympathetic-
Preganglionic cells will synapse with a Postganglionic cell in the ganglion.

CHOLINERGIC & ADRENERGIC FIBERS

▪︎Sympathetic & Parasympathetic nerve fibers- secrete mainly either one of the 2 synaptic transmitters:
Norepinephrine & Acetylcholine.

 Adrenergic:
- Norepinephrine
- Sympathetic Postganglionic Neurons (except sweat glands & Blood vessels)
 Cholinergic:
- ACH (Acetylcholine)
- All Preganglionic neurons (symp & Parasymp)
- Parasympathetic Postganglionic Neurons
- Postganglionic sympathetic fibers to sweat glands and some blood vessels.

All Preganglionic- produce ach-like substances

All Postganglionic - activate ach-like substances

Almost all parasympathetic Postganglionic- produce ach

MECHANISMS OF TRANSMITTER SECRETION & REMOVAL from synapse

o Secretion of ACH and Norepinephrine by Postganglionic Nerve Endings

● Many parasympathetic & almost all Sympathetic nerve fibers touch the effector cells of the
organs.
● Bulbous Enlargement- overpass, they don’t touch.
● Varicosities – transmitter, vesicles of ACH & Norepinephrine is synthesized and STORED.
- have presence of a large # of mitochondria (provide ATP)

SYNTHESIS OF ACH, ITS DESTRUCTION AFTER SECRETION, AND ITS DURATION OF ACTION

 Synthesis
Acetyl-CoA + Choline --------------> Acetylcholine (process: Choline Acetyltransferase)
▪︎synthesized in the terminal endings in Varicosities
▪︎when ACH is released in to the tissue it will persist in the tissue for a few seconds while it
performs its nerve signal transmission functions
 Destruction
Acetylcholine ----------> Acetate + Choline (Process: acetylcholinesterase)
♤ Acetylcholinesterase – destroys ACH
♤ Will go back to be synthesized again

SYNTHESIS OF NOREPINEPHRINE, ITS REMOVAL, & DURATION OF ACTION

1. Tyrosine  Dopa (process: hydroxylation) *acts in cytoplasm*

2. Dopa  Dopamime (process: decarboxylation) *acts in cytoplasm*
3. Transport into Vesicles
4. Dopamine  Norepinephrine (process: hydroxylation)

In the Adrenal Medulla:

5. Norepinephrine  Epinephrine (process: methylation)

♡ Adrenal Medulla: produces Epinephrine & Norepinephrine

♡ Sympathetic Postganglionic Neurons not in the medulla produces only: Norepinephrine

Removed in 3 ways: removal of Norepinephrine in the synapse:

♡ Reuptake: 50-80% in the Adrenergic nerve endings

♡ Diffusion- away from the nerve endings into the surrounding and to the blood

♡ Destruction – very small amount of destruction – 2 enzymes:

- Monoamine oxidase – found in nerve ending

- Catechol-O-methyl transferase – found in tissues (liver)

2 ways for Norepinephrine to be released:

1. Synapse - Norepinephrine is active 10-30 secs

2. Blood vessels – activity declines 1min
RECEPTORS ON THE EFFECTOR ORGANS

 When norepi or ach binds it Change in membrane permeability

 Activating or inactivating an enzyme attached to the other end of the receptor in the interior
 Before ach and norepi is secreted in the AN ending can stimulate first they need to bind to a
receptor found on the effector cells.
 Receptors are found on the outside of the membrane

EXCITATION OR INHIBITION BY CHANGING MEMBRANE PERMEABILITY

 The action potential (piso)

 In order to have an action potential we need stimuli (chemical, mechanical, or electrical)

RECEPTOR ACTION BY ALTERING INTRACELLULAR “2 ND MESSENGER” ENZYMES

 Binding an Epinephrine or Norepinephrine to the receptor will cause a change in the protein
that is inside that would activate or inactivate the cell
 Adenylyl cyclase- an enzyme inside protein receptor that will be activated if Epinephrine binds
to the receptor.

2 ways how neurotransmitters cause effects on organs are:

◇ receptors (opening by increasing or decreasing membrane permeability)

◇ alteration of 2ndary messenger found inside the cell attached in the receptor.

TWO PRINCIPAL TYPES OF ACH RECEPTORS

♧ Muscarinic Receptors

- All effectors stimulated by Postganglionic Cholinergic neurons

- G- Protein coupled Receptors (use 2 nd messenger)
- Anytime there is activation here, it will cause alteration of a protein found inside the receptor
- Found in all effector cells stimulated by the Postganglionic Cholinergic neurons (either sympa or
parasympa NS)

♧ Nicotinic Receptors

- Synapse between Preganglionic and Postganglionic Neurons

- Ligangated ion channels
- All postganglionic Receptors will contain Nicotinic Receptors
- All Preganglionic produce ACH

ALPHA AND BETA ADRENERGIC RECEPTORS

2 major classes:

 Alpha- A1, A2; linked to 2nd messengers

 Beta - B1, B2, B3; also use 2nd messenger protein
 Norepinephrine- excites A>B
 Epinephrine- excites A=B
  Alpha Receptors- the action is both Epinephrine and Norepinephrine
 Beta Receptors- actions is Epinephrine than Norepinephrine.

NOTE: - certainly, Alpha functions are mostly EXCITATORY and also INHIBITORY

- Alpha and beta Receptors are does not mean that they are inhibitory or excitatory but it
depends upon the affinity of the hormone for the receptors in a given effector organ.
- SYMPATHETIC Stimulation causes excitatory effects in some organs buts inhibitory in others.

EFFECTS OF SYMPATHETIC AND PARASYMPATHETIC STIMULATION ON SPECIFIC ORGANS

 Eyes – controlled by the ANS

• Pupillary dilation (SymNS) excited during danger/protective; constriction when there is excess
light (ParasymNS)
• Focusing the lens (ParasymNS only)
 Glands
• Nasal, lacrimal, salivary, & many GI glands (ParasymNS) cause watery secretions; (SymNS)
concentrated secretion with hight % of enzymes and mucus however can reduce rate of
secretion.
• sweat glands (SymNS) Cholinergic fibers; Postganglionic produce ach; (ParasymNS) has no
activation
• apocrine (SymNS) Adrenergic (found in axilla and groin) produce odoriferous secretion due to
Norepinephrine. Functions as lubricant.
 Heart
• (SymNS) – increase overall activity: increase HR and force of contractions (when in shock: give
epi/norepi via IV)
• (ParasymNS) – decrease overall activity: decrease HR & strength of Contractions
 Systemic Blood Vessels
• most of systemic BV esp: abdomen, skin of limbs are constricted by (SymNS)
• Skin and viscera cause vasoconstriction (contains more Alpha Receptors)
• heart contains a lot beta Receptors and cause Vasodilation
• ParasymNS Stimulation has no effect in Blood vessels
• A> B
 Arterial Pressure
• determined by 2 Factors:
1. Propulsion of blood by the heart
2. Resistance the blood flow through the peripheral vessels
• BP = Stroke Volume × Peripheral Vascular Resistance (factors contribute to BP)
• SV – amount of blood coming out of the ♡ each beat
• Peripheral Vascular Resistance- the resistance the blood has to overcome in order for the
blood to come out from the heart.
• (SymNS) Stimulation will increase both Propulsion by the heart and resistance to flow due to
vasoconstriction periphery (not a long-term effect)
• moderate (ParasymNS) Stimulation via VAGAL NERVES will decrease the pumping & HR
• very strong (ParasymNS) Stimulation via vagal nerves can stop the heart entirely for a few
seconds / temporary loss of all arterial pressure
FUNCTION OF ADRENAL MEDULLAE – contains modified Postganglionic Neurons came from embryonic
development

- Stimulation of (SymNS) cause large quantities of the production of these 2 into the blood:
o Epinephrine- 80% secretion as norepi is converted to epi in the medulla
○ greater cardiac Stimulation
○ cause weak constriction
○ action lasts 5-10× greater metabolic effect
○ has more beta Receptors alpha
○ A=B
o Norepinephrine- 20%
○ Circulation will cause vasoconstriction because it has more alpha than beta of the BV
○ increases activity of the heart
○ inhibits the GI tract
○ dilates pupils of the eye
○ more Alpha than beta

THE ADRENAL MEDULLAE SUPPORT SYMPATHETIC NERVOUS SYSTEM FUNCTIONS

 Destruction of one will cause transient loss of SymNS function due to the presence of the other.
 2 ways of Stimulation of organs
1. Directly by the SymNS nerves that terminate in the organ
2. Indirectly by the Adrenal Medulla
 Stimulation of the medulla will support SymNS action and the SymNS will support the action of
the medulla
 The loss of 2 adrenals (epi&norepi) in the blood will have little effect in the SymNS.

TONE – allows a single NS to increase and decrease activity of an organ

Ex:

 Sympathetic- Blood vessels

♤ will normally keep most of the arterioles/arteries of the body CONSTRICTED to about ½ of
their maximum diameter.
♤ by increasing the degree of Stimulation the vessels will constrict more
♤ decrease in sympathetic tone will increase in vasodilation
♤ can cause constriction and dilation by itself increasing or decreasing the tone.
 Parasympathetic- GI tract
♧ removal of Parasympathetic to the gut / cutting the vagus nerve to the gut will cause serious
prolonged intestinal atone. Will result blockage in colon/constipation.

BASAL SECRETION OF EPINEPHRINE AND NOREPINEPHRINE

 By Adrenal Medullae (secrete epi and norepi)

 Denervation – lose of SymNS & ParasymNS tone
♡ BV – vasodilation (5-30s) 》intrinsic BV compensation & increased sensitivity to epi and
norepi from adrenals 》almost normal vasoconstriction (quick compensation)
 ♡ GI and Heart – ParasymNS- longer compensation (no support); w/o ParasymNS there’s
increase in HR, will only decrease after a few months (when compensation is over).

SUPERSENSITIVITY AFTER DENERVATION

 Denervation supersensitivity
◇ up to 10 fold increase in sensitivity
 Organ becomes sensitive to the injected epi&norepi

AUTONOMIC REFLEXES

 Cardiovascular
□ Baroreceptor Reflex – Baro mean pressure
- detects pressure
- found in aorta and internal carotids (neck)
- high pressure > stretching of BV > which will stimulate Baroreceptor > elicit baroreceptor
reflex > inhibit sympathetic impulses that goes in the ♡ and blood vessels > excite
Parasympathetic > decrease in arterial pressure and HR
 GI – upper part and rectum is controlled by autonomic reflexes
□ Rectal stretch – defecation
□ food – salivation
□ smelling, seeing presence of food will cause to send signals to vagal, glossopharyngeal, and
salivatory nuclei found in brainstem.
- Stimuli 》Brainstem 》transmit signals through ParasymNS 》secretion of glands in the mouth,
stomach.
- rectum stretch 》initiation of Sensory impulses to spinal cord 》bring back reflex signals to the
ParasymNS S2, S3 》increase in peristalsis 》expulsion of poop 》defecation.

Other Autonomic Reflexes

 Bladder Stretching – urination (same function from rectum)

 Male reproduction
♤ ParasymNS- erection
♤ SymNS - ejaculation

MASS DISCHARGE

♧ phenomenon where all portions of the SymNS will simultaneously discharge as a complete unit.

♧ happens when Hypothalamus is activated by fright, fear, or severe pain.

♧ result is widespread reaction in the body called ALARM / STRESS RESPONSE

ALARM / STRESS RESPONSE

♡ Increase BP

♡ Increase blood to active muscle and Decrease to GI tract and kidneys

♡ Increase cell metabolism

♡ increase blood glucose

♡ glycolysis

♡ Increase muscle strength

♡ Increase mental activity

♡ rate of coagulation (protective)

SymNS- mental or physical stress excites

- Provide extra activation when in stress

- Signals downward
- Fight or flight response

Sympathetic System Selective Stimulation

 Sweating – heat regulation (cholinergic fiber)

 Local reflex – vasodilation
 GI Functions- passing to the gut, does not affect other parts of the body

SPECIFIC LOCALIZED RESPONSES OF ParasymNS

o Heart- changes in rate only

o Rectal emptying -> bladder emptying
o Salivation-> gastric secretion

PHARMACOLOGY OF AUTONOMIC NS (Clinical Applications)

 Sympathomimetic Drugs – Mimic: act on A and B receptors

♤ Drugs that act on adrenergic effector organs
♤ AKA Adrenergic drugs
♤ Norepinephrine- A>B more vasoconstriction
♤ Epinephrine- A=B less vasoconstriction
♤ Methoxamine – A
♤ Phenylephrine- A more more vasoconstriction
♤ Isoproterenil- B vasodilation
♤ Albuterol – only B2 (ASTHMATICS) primary bronchodilation

DRUGS CAUSE RELEASE OF NOREPINEPHRINE (indirect Sympathomimetic actions)

1. Ephedrine
2. Tyramine
3. Amphetamine

◇ Their effect is to cause release of Norepinephrine to the vesicles. Increase release of Norepinephrine.

DRUGS THAT BLOCK ADRENERGIC ACTIVITY

 Points Blocked
 The synthesis and storage of norepi in nerve endings- reserpine
  Release of Norepinephrine - guanethidine
 A receptor blockade:
□ A1 and A2 – phenoxybenzamine & phenotalamine
□ A1 only – prazosin and terazosin
□ A2 – yohimbine
 B Receptor blockade:
□ B1 and B2 - propranolol
□ B1 – atenolol, nebivolol, and metoprolol
 Blockade of transmission of impulse through autonomic ganglia- hexamethonium & pentolinium

DRUGS ACT ON CHOLINERGIC EFFECTOR ORGANS

o Parasympathomimetic Drugs – mimic ParasymNS

♧ AKA Cholinergic Drugs
♧ ACH- rapidly destroyed

2 most commonly used Cholinergic drugs: (acts directly Muscarinic Receptors)

♧ Pilocarpine – M
♧ Metacholine – M

ANTICHOLINESTERASE DRUGS – Indirectly act on Parasympathetic receptors BUT POTENTIATE ACH

 Drugs that have Parasympathetic potentiating effect

 Neostigmine, pyridostigmine, & ambenonium
 Inhibit acetylcholinesterase

ANTIMUSCARINIC DRUGS

 Block the action of ACH on the Muscarinic type of Cholinergic effector organs
 Atropine, homatropine, scopolamine
 Do not affect nicotinic receptors of ACH in Postganglionic Neurons or skeletal muscles.