10, 11 and 12 - Autonomic Nervous System Flashcards
What is the autonomic nervous system?
The portion of the nervous system that controls most visceral functions and accommodates coordinated responses to external stimuli
Are autonomic disorders being sufficiently considered, suitably investigated and appropriately managed in clinical practice?
NOOOOOO
What accounts for these issues with ANS disorders?
Symptoms are so variable
What does the central nervous system consist of?
Brain
Spinal cord
What does the peripheral nervous system consist of?
Somatic nervous system
Autonomic nervous system
What are the two parts of the somatic nervous system?
Somatic efferent nerves which innervate skeletal muscles
Somatic and visceral afferent nerves
What are the three components of the autonomic nervous system?
Sympathetic division (SANS) Parasympathetic division (PANS) Enteric division (which is closely interconnected with SANS and PANS)
In the sympathetic division of the ANS, the preganglionic fibers are _________ compared to the postganglionic fibers.
Short
In the parasympathetic division of the ANS, the preganglionic fibers are ________ compared to the postganglionic fibers
Long
long pre, short post
Why do parasympathetic fibers have longer presympathetic fibers?
Because they synapse in the wall of the visceral organs, so they have to travel a long way to get there (long pre) but they are very close after they synapse (short post)
What is the one exception to the two-neuron organization of the ANS? (meaning there is a pre and post ganglionic nerve)
The adrenal medulla
Why is the adrenal medulla an exception?
It is considered to be a giant ganglion that does not have post-gaglionic fibers (there fore there is only one nerve, the presynaptic nerve)
What does the adrenal medulla release?
- Epinephrin
- Norepinephrin
- Dopamine
- Peptides
Where are these neurotransmitters released?
Directly into the blood stream
Is activation of the ANS involuntary or voluntary?
Involuntary
Can responses to a stimuli in the ANS be excitatory, inhibitory or both?
Both
What spinal levels contribute to the sympathetic division of the ANS?
The throaco-lumbar section (T1-L3,4) as well as some cranial nerves
At the spinal level, where do the autonomic neurons lie?
The intermediolateral cell column (AKA lateral horn)
Where is the intermediolateral cell column located?
Between the dorsal and ventral horns
Where do axons from preganglionic sympathetic neurons exit the spinal cord?
VENTRAL roots along with axons from somatic motor neurons
From the ventral root, the preganglionic sympathetic neurons branch away from the somatic motor neurons and enter the ____________
White communicantes
Why is the white communicantes white?
Because most preganglionic sympathetic axons are myelinated, making the white communicantes appear white
What is a paravertebral ganglia?
Along the length of the sympathetic trunk are ganglia known as paravertebral ganglia. The ganglia are distinguished as cervical, thoracic, lumbar, and sacral and, except in the neck, they closely correspond to number to the vertebrae.
What is a prevertebral ganglia?
Sympathetic ganglia which lie between the paravertebral ganglia and the target organ
What is the specialized ganglia?
There are four:
- Superior cervical ganglion
- Celiac ganglion
- Superior mesenteric ganglion
- Inferior mesenteric ganglion
There are three modes of innervation in the sympathetic division of the ANS. What are they?
The preganglionic neuron goes to the…
1 - paravertebral OR prevertebral ganglion then becomes a post-ganglionic neuron which then goes to the target organ
2 - specialized ganglion then goes to the target organ
3 - organ directly (adrenal medulla)
The parasympathetic division of the ANS emerges from two separate regions of the CNS. What are they?
CRANIO-SACRAL
What does the cranial outflow consist of?
Preganglionic fibers in certain cranial nerves
Which cranial nerves contain parasympathetic fibers?
Oculomotor nerve
Facial and glossopharyngeal nerves
Vagal nerve
Where do the ganglia for parasympathetics coming from cranial outflow lie?
The ganglia lie close to the target organs
What does the sacral outflow consist of?
Parasympathetic fibers destined for the pelvic and abdominal viscera emerge from the spinal cord ina bundle of nerves known as the nervi erigentes
Where are these parasympathetic fibers destined for?
- Bladder
- Descending large intestine
- Rectum
- Genetalia
Where do the sacral outflow of parasympathetic nerve synapse?
In scattered pelvic ganglia
What is unique about the pelvic ganglia?
They carry both sympathetic and parasympathetic fibers - the two divisions are NOT anatomically distinct in the pelvic region
What is the enteric nervous system?
A collection of nerve plexuses that surround the gastrointestinal tract, including the pancreas and biliary system
We say that the enteric nervous system is “sandwhiched” between the ______________
The layers of the gut
The enteric nervous system is connected by a ____________
Dense meshwork of nerve fibers
What does the myenteric plexus of the enteric nervous system control?
Motility
What does the submucosal plexus of the eteric nervous system control?
Ion and fluid transport
Where does the enteric nervous system receive input from?
Both the sympathetic and parasympathetic divisions
Can the enteric nervous system funciton normally WITHOUT extrinsic input?
YES!
One of the characteristics of the autonomic nervous system is DUAL INNERVATION. What does this mean?
***
Most organs receive both sympathetic and parasympathetic innervation, meaning that the actions of the organ are controlled by BOTH systems
What are the exceptions to the dual innervation?
ONLY sympathetic
- Hair follicles
- Thermoregulatory sweat glands
- Liver
- Adrenal glands
- Kidney
There is one place in the body where the sympathetic and the parasympathetic innervations produce SIMILAR rather than opposing effects. Where is this?
Salivary glands
How many somatic nerves release acetylcholine?
ALL OF THEM
How many of the preganglionic fiers of the ANS release acetylcholine?
ALL OF THEM
Do all post-ganglionic fibers have the same receptors and respond the same way to ACh?
No…
What receptor is found at all of the ganglion?
Nicotinic receptors
Where does the variability come from?
You will have a different response based on the receptors on the target organs
What do parasympathetic POSTganglionic fibers release? (we know their preganglionic fibers release ACh)
Post ALSO release ACh
What do sympathetic POSTganglionic fibers release?
They are andrenergic (epinephrine/norepinephrine) or dopaminergic (dopamine)
At what part of the body are postganglionic sympathetic fibers dopaminergic (release dopamine)?
Renal vascular smooth muscle
What is the exception to the rule of postganglionic sympathetic fibers?
Thermoregulatory sweat glands
What do postganglionic sympathetic fibers release at sweat glands?
Acetylcholine because the sweat glands possess muscarinic (muscle) receptors (meaning they respond to acetycholine)
What does cholinergic neurotransmission mean?
Its a shorter way of saying acetylcholine neurotransmission
There is a general four step method of cholinergic neurotransmission. What is it?
1 - Synthesis of the neurotransmitters at the pre-synaptic terminal
2 - Storage of the neurotransmitter
3 - Release of the neurotransmitterand actions of the transmitter at the receptor sites
4 - Termination of the transmitter’s action
What are the three steps that happen in the initial synthesis step of cholinergic neurotransmission?
Occurs at the presynaptic terminal…
1 - Uptake of choline by the choline transporter (CHT)
2 - Conjugation of acetylCoA (mito) plus choline with the enzyme choline acetyltransferase (ChAT)
3 - Final product of acetylcholine is formed
There is an experimental drug being tested that blocks the synthesis of acetylcholine. What step does it function at?
The uptake of choline - it blocks the choline transporter (CHT)
What is the enzyme that conjugates the acetylCoA to the choline?
Cholineacetyltransferase (ChAT)
Describe the storage step in cholinergic neurotransmission
ACh is transported into a storage vesicle by a second carrier called the vesicle-associated transporter (VAT) where it remains until secretion
What experimental drug is working to prevent acetylcholine storage?
Vesamicol
It attempts to block the VAT or vesicle-associated transporter
What is the first step in the release of acetylcholine from a presynaptic terminal
Depolarization of the nerve terminal
What happens after the presynaptic termianl has been depolarized?
Voltage-dependent Ca++ enters the presynaptic terminal
What does the Ca++ do once it enters the terminal?
Binds to calmodulin
What does the Ca++ calmodulin complex associate with (2 things)
VAMP (vesicle associated membrane proteins)
SNAP (synaptosome associated proteins)
Botulinum toxin functions at this point during the release of acetylcholine. What does it block?
SNAPs - synaptosome-associated proteins
What is the final step of acetylcholine release?
The vesicles fuse to the membrane and the neurotransmitter is released via exocytosis
The action of acetylcholine must be terminated once it has had a chance to function… How is it terminated?
First, rapid hydrolysis of ACh to form choline and acetate
Second, choline re-uptake into the terminals
What cleaves the ACh into acetate and choline?
Acetylcholine esterase (AChE)
What blocks the cleavage action of AChE?
AChE inhibitors
Receptors for acetylcholine fall into two categories. What are they?
1 - Muscarinic receptors
2 - Nicotinic receptors
What type of receptors are muscarinic receptors?
G protein receptors
What happens when the type of G protein in a muscarinic receptor is different?
You get a different response
What are nicotinic receptors?
Transmembrane ion channels that consist of five subunits forming a funnel around the mouth of a central core
What happens to a nicotinic receptor when ACh is bound?
The mouth of the channel is closed
What happens when more than ACh is bound to a nicotinic receptor?
- Conformational change
- Opening of the channel
- NA+ and K+ flow down their gradients
- NA+ influx can create a depolarization and action potential leading to muscle contraction
There are two autonomic activities of the eye that we discussed. What are they?
Aqueous humor production
Autonomic pupil sphincter control
What type of muscarinic receptor is activated in the eye during these two activities?
M3 receptor
Aqueous humor is produced by…
The epithelium of the ciliary processes
What are the processes of the pupil sphincter?
- Ciliary muscle allows for near accommodation and the opening of the canal of Schlemm (parasympathetics)
What type of receptors would you find in the heart?
M2 receptors predominate, but M3 receptors are also present
What is the heart regulated by? Simulation or inhibition?
INHIBITION
Know this
What does it mean that the heart is regulated by inhibition?
If you ACTIVATE the parasympathetics of the nervous system, you DECREASE the cardiac activity
What are the effects of decreasing cardiac activity?
Slow heart reaction, slow contraction of the heart muscles
This is why we rub the eyes to slow the heart
What type of receptors are found in the vesicular bladder?
A LOT of M3 receptors
If a patient is overdosing on M3 receptor drugs, what is a symptom you will see?
Incontinence and problems with voiding
Activation of an MC receptor in the bladder facilitates urination by…
Contracting muscles
Relaxing the trigone
Inhibiting the sphincter
Is vascular smooth muscle innervated the same or differently from visceral smooth muscle?
Different
How is visceral smooth muscle innervated?
Just by nerve innervation
How is vascular smooth muscle innervated?
By BOTH nerve input and endothelial input
What is vascular tone controlled by?
Perivascular nerves as well as endothelial factors
What happens when an M3 muscarinic receptor is activated in a blood vessel?
It depends on whether or not the endothelium is in tact
What happens when an M3 muscarinic receptor is activated in a blood vessel with an INTACT endothelium?
VASODILATION
What causes the vasodilation?
Effects of M3 activation on endothelial cells leads to production of endothelium-derived relaxing factors
What happens when an M3 muscarinic receptor is activated in a blood vessel with a DAMAGED endothelium>
VASOCONSTRICTION
What causes the vasoconstrictuion?
Direct effects of M3 activation on vascular smooth muscle cells causes vasoconstriction (unopposed by NO produced from endothelial M3 activation)
What type of muscarinic receptors are found in sphincters?
M3
What is the effect of the activation of an M3 receptor found in sphincters?
Mostly relaxation
What is the exception to this rule?
The lower esophageal sphincter contracts
What type of muscarinic receptors are found in glands?
M3
What is the effect of the activation of an M3 receptor found in a gland?
Secretion (sweat for thermoregulation)
Salvation
Lacrimation
How would you damage an endothelium so that vasoconstriction would occur instead of vasodilation of vessels?
Smoking
High cholesterol
Diabetes
What types of ganglia have nicotinic receptors?
Autonomic ganglia
What is the net effect of ganglionic nicotinic receptor activation?
This depends on the balance the ganglia has between sympathetic and parasympathetic innervation
Where would you find Nn nicotinic receptors?
AdreNal medulla
AutoNomic ganglia
Where would you find Nm nicotinic receptors?
NeuroMuscular junction
What is the response when the Nn nicotinic receptor is activated at the adrenal medulla?
Secretion of epinephrin and norepinephrine
What is the response when the Nn nicotinic receptor is activated at the autonomic ganglia
Simulation
The net effects depend on PANS/SANS innervation and DOMINANCE
What is the effect when the Nm nicotinic receptor is activated at a neuromuscular jucntion?
Stimulation
Twithc, hyperactivity of skeletal muscle
Are Nm and Nn the same thing?
No - they are similar but not identical pharmacologically
Case study: flower causing pupil to dilate
Inhibition of M3 receptor on pupil
The sphincter inhibits parasympathetics
No contraction of the pupil is possible
DIlation is seen
What is andrenergic neurotransmission?
Andrenergic neurons also transport a precursor molecule into the nerve ending, then synthesize the catecholamine transmitter, and finally store it in membrane-bound vesicles
Is the process of catecholamine synthesis more complicated or simple in the adrenergic neurons?
Complicated
What is the rate limiting step in catecholamine synthesis?
The conversion of tyrosine to dopa
What inhiits the rate limiting step of catecholamine synthesis?
A tyrosine analog - METYROSINE
Know this
What is the final produc in most sympathetic postganglionic neurons?
Norepinephrine
In the adrenal medulla and certain areas of the brain, norepinephrine is further converted into ___________
Epinephrine
What is the general path to forming the catecholamines?
Tyrosine –> Dopa –> Dopamine –> Norepinephrine –>Epinephrine
This is ONLY in the adrenal medulla
Once the catecholamines are formed, they must be stored. How does this happen?
Synthesized catecholamines are transported into vesicles by VMATs (vesicular monoamine transproters)
What can inhibit VMATs?
Reserpine *
WHat does reserpine cause?
Depletion of the transmitter stores
Where does the conversion of norepinephrine to epinephrin take place
In the vesicles if the enzyme is available
How are catecholamines released from the presynaptic terminal?
Similar to the release of ACh from cholinergic nerve endings
How does termination of the action of catecholamines occur?
Occurs by multiple mechanisms
- Simple diffusion
- Neuronal reuptake
- Extraneuronal uptake
Describe simple diffusion
Catcholamines diffuse into the circulationa nd are metabolized
Describe neuronal reuptake ***
Catecholamines are taken up at nerve terminals by solute carriers
Norepinephrine = transporter is norepinephrine transporter, NET
What does NET do?
It carries norepinephrine and similar molecules back into the cell cytoplasm from the synaptic cleft
What else do we call NET?
Reuptake 1 or uptake 1
What can inhibit NET?
Cocaine
Tricyclic antidepressant drugs
What is the result of inhibiting NET?
Increase of transmitter activity in the synaptic cleft (prolonged activity)
Describe extraneuronal reuptake
Catecholamines are taken up via extraneuronal transproters (ENT)
What can inhibit ENT?
Many pharmacological agenst such as corticosteroids
What type of receptors are adrengeric receptors?
G protein-coupled receptors
What is the clinical significance of the adrenergic alpha one receptor?
If you block it, you will see vasodilation and a decreased blood pressure - you can use this clinically
What happens when the Ca++ increases near the adrenrgeric alpha one receptor?
Vasoconstriction
What happens when the alpha 1 adrenergic receptor is activated in the eye?
KNOW THIS
Contraction (the radial (dilator) muscle is affected)
This will lead to mydriasis
What happens when the alpha 1 adrenergic receptor is activated in the arterioles of the skin and viscera?
Contraction
This will lead to high diastolic pressure and high afterload
What happens when the alpha 1 adrenergic receptor is activated in the veins?
Contraction
This will lead to high venous return and high preload
What happens when the alpha 1 adrenergic receptor is activated in the bladder trigone and spincter?
Contraction
This will lead to urinary RETENTION
What happens when the alpha 1 adrenergic receptor is activated in the male sex organ?
The vas deferens contracts and ejaculation doesn’t happen (erection is fine)
What happens when the alpha 1 adrenergic receptor is activated in the liver?
High glycogenolysis
What happens when the alpha 1 adrenergic receptor is activated in the kidney?
Low renin release
What happens when the alpha 2 adrenergic receptor is activated in the prejucntional nerve terminal?
Lower rate of transmitter release and norepinephrine sythesis
What happens when the alpha 2 adrenergic receptor is activated in the platelets?
Aggregation
What happens when the alpha 2 adrenergic receptor is activated in the pancreas?
Decreased insulin secretion
What happens when the beta 1 adrenergic receptor is activated in the SA node of the heart?
Heart rate goes up
What happens when the beta 1 adrenergic receptor is activated in the AV node of the heart?
Increase in the conduction velocity
What happens when the beta 1 adrenergic receptor is activated in the atrial and ventricular muscles?
The force of contraction, conduction velocity, cardiac output and O2 consumption goes UP
What happens when the beta 1 adrenergic receptor is activated in the his-purkinje system?
There is an increase in the automaticity and conductio velocity
What happens when the beta 1 adrenergic receptor is activated in the kidney
Renin release increases
What happens when the beta 2 adrenergic receptor is activated in the blood vessels?
Vasodilation (distolic BP goes down)
What happens when the beta 2 adrenergic receptor is activated in the uterus?
Relaxation
What happens when the beta 2 adrenergic receptor is activated in the bronchioles?
Dilation
What happens when the beta 2 adrenergic receptor is activated in the skeletal muscle?
Glycogenolysis goes up and contractility goes up
What happens when the beta 2 adrenergic receptor is activated in the liver?
Glycogenolysis goes up
What happens when the beta 2 adrenergic receptor is activated in the pancreas
Insulin secretion goes up
What is the effect of dopaminergic receptor activation in the renal, mesenteric and coronary vasculature?
Vasodilation
What is the specific effect in the kidney?
High glomerular filtration rate
High renal blood flow
High sodium excretion
What is a homotropic interaction?
The transmitter, by binding to presynaptic autoreceptors, affects the nerve terminals from which it is being released
What is a heterotrophic interaction?
One neurotransmitter affects the release of another via actions on heteroreceptors
Example: Norepinephrine affects Ach release & vice-versa
There is a heterotrophic interaction in Parkinson’s disease. What is it?
Dopamine is reduced in Parkinson’s disease
The affect is that ACh is increased
How do you treat Parkinson’s knowing this?
Either restore the dopamine or inhibit the ACh
There are two observed examples of supersensitivity and hyperactivity in chemical transmission. What are they?
- When a nerve is cut, there is supersensitivity downstream
- When a ganglion is blocked for a period of time and then the blocker is removed, you will see hyperactivity of the organs due to supersensitivity
Why do we observe this supersensitivity? (2 reasons)
- There is a proliferation of receptors
- There is a loss of the mechanisms that remove the transmitter
How is this clinically relevant?
When you take someone off drugs for hypertension (adenoceptor blockers), you will see rebound hypertension following withdrawal of the meds
When else would we see this clinically?
When testing for an autonomic disorder…
If you give someone a low dose stimulation and they have an excessive response, they can be diagnosed with an autonomic disorder
What is cotransmission?
Neurons release more than one transmitter or modulator, each of which interacts with specific receptors and produces effects, often both pre- and postsynaptically.
There are two main functions of the autonomic nervous system. What are they?
1 - Assist the body in maintaining a constant internal environment
2 - Accommodate a coordinated response to an external stimuli
How does the ANS assist the body in maintaining a constant internal environment?
- Provides motor control for viscera
- Allows for smooth muscle, cardiac muscle and glands to be regulated
- Allows the autonomic fibers of the peripheral nerves to be accompanied by visceral afferent fibers (originate from sensory receptors in viscera)
How does the ANS accommodate a coordinated response to external stimuli?
Examples:
- Pupil response to ambient light
- Fight or flight response
Are sympathetic and parasympathetic nervous systems physiological opponents?
NO
***
What is the relationship between the sympathetic and parasympathetic nervous systems?
***
They each serve their own physiological function and can be more or less active in a particular organ or tissue according to the need of the moment
