Autonomic Nervous System Flashcards
(T/F?) Adrenergic Receptors can also bind Dopamine?
True
Define the ANS?
The ANS is the involuntary branch of the PNS that conducts impulses from brainstem or spinal cord to cardiac muscle, smooth muscle and glandular tissue.
Other names for the ANS
1) Visceral Nervous System
2) Involuntary Nervous System
3 Divisions of the ANS?
1) Sympathetic
2) Parasympathetic
3) Enteric (GI) Nervous system
The ANS regulates involuntary activities such as?
1) Visceral functions
2) Metabolic functions to maintain homeostasis
3) BP & HR
4) GI motility and secretion
5) Bladder emptying/filling
6) Sweating and temperature regulation
7) near/far vision and pupil size
8) secretions of certain endocrine glands
What role is the Enteric Nervous System responsible for within the ANS?
The processes of mixing, propulsion, and absorption of nutrients in the GI tract.
How does the ENS regulate digestive activity?
Via the mycenteric and the sub mucous plexi
(T/F?) Serotonin is also a neurotransmitter used by the ENS?
True
The ANS is regulated by which higher centers of the brain?
1) Hypothalamus - Acts as a signal relay and integration center
2) Medulla - Hemodynamic and ventilatory control
3) Pons - Hemodynamic and ventilatory control
Cholinergic Axon vs. Cholinergic Receptor?
1) Cholinergic Axon - A nerve fiber that secretes ACh
2) Cholinergic Receptor - A receptor that binds to ACh
Adrenergic Axon vs. Adrenergic Receptor
1) Adrenergic Axon - A nerve fiber that secretes NE
2) Adrenergic Receptor - A receptor that binds to NE or Epi
Preganglionic vs. Postganglionic?
1) Preganglionic - Cell body located CNS (brain or spinal cord) and carries msg to the autonomic ganglia, axon is myelinated, always releases ACh to a nAChR on the postganglionic cell.
2) Postganglionic - Cell body located outside the CNS (in an autonomic ganglion) and carries msg to the visceral effector organ, axon is unmyelinated, can release adrenergic or muscarinic.
Where are the sympathetic preganglionic neuronal cell bodies located?
In the intermediolateral of the spinal cord arising from T1 to L2 or L3 segments aka the Thoracolumbar outflow.
Characteristics of the sympathetic preganglionic fibers?
1) They are short
2) Myelinated
3) They synapse in the sympathetic autonomic ganglia
4) 22 pairs of ganglia that lie on either side of the vertebral column
Postganglionic fibers primarily release NE as their neurotransmitter, except for the following…?
1) Sweat glands - Release ACh to mAChr
2) Blood Vessels - ACh is released to mAChr on skeletal muscle
(T/F?) The ratio of sympathetic pre to postganglionic fibers is 1:20?
True - preganglionic fibers issuing from the spinal cord may synapse with neurons of more than one sympathetic ganglion: aka defuse innervation.
Effects of the sympathetic nervous system?
1) Increase HR, BP and CO
2) Bronchodilation
3) Shunts blood away from intestines and other organs to muscles
4) Increase Blood glucose
Where are the cell bodies of the parasympathetic preganglionic fibers located?
At the brainstem and sacral S2 to S4 spinal nerves: aka the Craniosacral outflow.
Characteristics of the parasympathetic Preganglionic fibers?
1) They are long
2) Myelinated
3) Releases ACh to nAChr
Characteristics of Parasympathetic postganglionic fibers?
1) They are short
2) They release ACh to mAChr
The ratio of parasympathetic pre to posganglionic fibers is 1:1. Whats the exception?
The ratio of preganglionic vagal fibers to ganglion cells in the myenteric plexus is 1:8000.
Function of the following Cranial Nerves:
1) CN III (Oculomotor)
2) CN VII (Facial)
3) CN IX (Glossopharengeal)
1) CN III - Innervate the eye orbit
2) CN VII - Innervate the lacrimal, nasal, submaxillary and sublingual glands
3) CN IX - Innervate the parotid gland
List of anatomies under the control of CN X (vagus)?
1) Heart
2) Lungs
3) Esophagus
4) Stomach
5) Small intestine and upper colon
6) Liver and spleen
7) Gallbladder
8) Pancreas
9) Upper portions of the uterus
(T/F?) The parasympathetic nervous system is functionally more selective, discrete, and localized than the sympathetic nervous system?
True
Synthesis, storage and release of ACh occurs in the cytoplasm of______?
1) Preganglionic SNS and PSNS nerves
2) Postganglionic PSNS nerves
3) Postganglionic SNS nerves innervating sweat glands and certain blood vessels.
4) Skeletal NMJ
Effects of Botulinum Toxin on the ACh synthesis, storage and release process?
Botulinum Toxin blocks vesicular fusion and exocytosis release of ACh.
(T/F?) ACh, once released into the synaptic cleft, can also act on the presynaptic mAChR or nAChR to modify its own release?
True - This is in addition to binding to the mAChR or nAChR on the posynaptic cell.
Describe the metabolic/degredation of ACh?
Acetylcholinesterase (AChE) is the enzyme responsible for hydrolysis of ACh to choline and acetate. Choline is transported back into the nerve ending, where it is used for synthesis of new ACh.
Where are AChE found?
In the synapses of cholinergic neurons and postsynaptic end plates of the NMJ.
How fast can AChE hydrolyze ACh?
1 molecule of AChE can hydrolyze an estimated 30,000 molecules of ACh every minute into choline and acetate.
Besides AChE, which other enzyme breaks down ACh? Where is it found and what’s is primary significance to CRNAs?
Butyrylcholinesterase aka pseudocholinesterase or plasma cholinesterase. It’s mostly found in liver and plasma but also in low concentrations near ACh receptors. It is VERY important in the metabolism of Succynlcholine and Mivacurium.
Characteristics of Choligernic receptors?
1) Binded by ACh only
2) 2 Types - Nicotinic and Muscarinic
Nicotinic vs. Muscarinic?
1) Nicotinic - Ligand gated (allows permeability to Na+, Ca+, and K+ ions resulting in depolarization and excitation), fast responses, 2 types (Nn and Nm)
2) Muscarinic - G-protein coupled receptors, slow responses.
Location on Nn vs Nm Nicotinic Receptors?
1) Nn are located in the autonomic ganglia, adrenal medulla, and CNS
2) Nm are located in the NMJs of skeletal muscles.
(T/F?) 2 molecules of ACh must bind in order to activate the receptor?
True
Which subtype of Muscarinic receptors are predominately found in the following areas:
1) Heart
2) Detrusor of the bladder
3) CNS
1) Heart - M2
2) Detrusor of the bladder -M3 (Contracts detrusor and relaxes trigone and sphincter)
3) CNS - All subtypes
Muscarinic Receptors are primarily located at?
1) Peripherally in organs and tissues innervated by parasympathetic postganglionic neurons
2) Sweat glands and blood vessels innervated by sympathetic posganglionic neurons
3) Autonomic ganglia
4) Vascular endothelial cells
5) CNS, hippocampus, cortex and thalamus
What are the 5 subtypes of mAChR’s and which proteins are they linked to?
1) M1 - Linked to Gq protein
2) M2 - Linked to Gi and Go proteins
3) M3 - Linked to Gq
4) M4 - Linked to Gi and Go proteins
5) M5 - Linked to Gq protein
Where are the 5 subtypes of mAChR’s located?
1) M1 - CNS, autonomic ganglia, glands (gastric and salivary).
2) M2 - CNS, SA, and AV node of heart, smooth muscle, autonomic nerve terminals and salivary glands (Atropine = non-selective M1 and M2 Antagonist).
3) M3 - CNS, abundant in smooth muscle, (airway smooth muscles, blood vessels), abundant in exocrine glands, some found in heart)
4) M4 - Preferentially expressed in CNS
5) M5 - Predominant in substantia nigra.
* Odds (m1,m3,m5) are Gq linked and evens are not
(T/F?). M1, M3, and M5 receptors couple the same Gq protein and signal through similar transduction pathways involving phospholipase C activity?
True - Via the generation of second messenger diacylglycerol (DAG) or Inositol Triphosphate (IP3) or cAMP.
IP3 vs. DAG
1) IP3 causes increase in the release of intracellular calcium causing contraction of smooth muscle and secretion.
2) DAG activates protein kinases which results in various physiological responses.
Effects of M2 and M4 binding to the Gi and Go proteins?
Gi and Go proteins are inhibitory and therefore signal through similar pathways that inhibit adenylyl cyclase leading to a decrease in cAMP or activation of inwardly rectifying K+ channels at the target site. These effects cause hyper polarization and inhibitory responses in effector organs.
Explain the physiological effects of ACh at the mAChRs in the following locations:
1) Heart
2) Respiratory tract
3) Urinary tract
4) GI tract
5) Miosis, Salivation/Lacrimation
1) Heart - Bradycardia, decrease in conduction velocity in SA and AV nodes, decrease in force of contraction.
2) Respiratory tract - Bronchoconstriction, increased bronchial secretions.
3) Urinary tract - Detrusor muscle contraction
4) GI tract - Enhanced gastric secretions, hyperpperistalsis
5) Miosis, Salivation/Lacrimation
3 Examples of Anticholinergic drugs?
1) Atropine
2) Scopolamine
3) Glycopyrrolate
What is a Sympathomimetic?
A drug that mimics the actions of Adrenergics.
What is the opposite of a Sympathomimetic called?
Sympatholytics
What is a Catecholamine?
An adrenergic or Sympathomimetic drug derived from phenylalanine, which is the amino acid precursor to Tyrosine.
What are the 3 Endogenous Catecholamines?
1) Epinephrine (aka adrenaline)
2) Norepinephrine (aka noradrenaline)
3) Dopamine
What are the 5 steps of Catecholamine Synthesis?
1) Tyrosine is transported into the presynaptic nerve terminal and converted by Tyrosine Hydroxylase (aka Tyrosine-3-Monooxygenase) to L-DOPA.
2) L-DOPA is then converted into Dopamine
3) Dopamine is then transported into synaptic vesicle by the vesicular monoamine transporter (VMAT-2)
4) Dopamine is converted into NE
5) NE is converted to Epinephrine
What is the “Rate Limiting Step “ in the Catecholamine Synthesis Process?
When Tyrosine is being converted to L-DOPA
Where does the final step of the Catecholamine Synthesis pathway happen and why?
The final step of converting NE to Epi occurs only in the adrenal medulla and in a few epi-containing neuronal pathways in the brainstem since they have the enzyme Phenylethanolamine-N-Methyltransferase.
Why is Epinephrine NEVER released from nerve terminals?
Epinephrine is a hormone, not a neurotransmitter.
Results of NE that’s already been released into the synapse rebinding to receptors on the presynaptic membrane?
1) Alpha2 receptor binding on the presynaptic membrane causes inhibitory response which diminishes further NE release.
2) Beta receptor binding on the presynaptic membrane causes stimulatory response which increases rerelease of NE back into synapse.
Which membrane protein is responsible for the Neuronal Re-uptake of NE back into the presynaptic cell and which drugs block the its action?
Norepinephrine Transporter (NET). The actions of NET are blocked by drugs like cocaine, venlafaxine, and TCAs.
3 ways in which endogenously released NE is terminated at the synaptic cleft? Which mechanism is more efficient?
1) Diffusion out of the synaptic cleft away from receptors
2) Reuptake into the presynaptic terminal via NET (Most efficient and responsible for 87% of NE termination)
3) Metabolism via Monoamine Oxidase (MAO) or Catecholamine-O-Methyltransferase (COMT).
Once NE is undergoes re-uptake via NET into the pre-synaptic cell, what happens to it?
Once transported back into the cytosol, NE is re-stored in vesicles or metabolized by MAO.
Which membrane protein is responsible for the Neuronal uptake of NE into the Postynaptic cell?
ENT
What is the final product of Catecholamine Metabolization?
The primary metabolite is vanillyl mandelic acid (VMA), which can be measured in a 24-hr urine collection for diagnostic purposes such as pheochromocytoma.
(T/F?) All adrenergic receptors are G-protein-coupled receptors?
True
(T/F?) Dopamine receptors are adrenergic receptors but are not a part of the ANS.
True
What are the two types of Alpha adrenergic Receptors, which proteins regulate them, and what kind of stimulus do they produce?
1) Alpha1 Receptors - Gq protein coupled and usually produces an excitatory response.
2) Alpha2 Receptors - Gi protein coupled and usually produces an inhibitory response.
What is the mechanism of action of precedex?
Precedex is a central alpha2 agonist and has the opposite effect of NE.
Which protein regulates the Beta-adrenergic receptors and what happens after the binding?
All Beta Adrenergic receptors are Gs -coupled proteins and activate adenylyl cyclase, which increases cAMP levels in cells.
What are the 3 types of Beta-adrenergic receptors and where are they found?
1) Beta1 - Found in kidney and heart and produces positive inotropic, chromotropic, and dromotropic effects.
2) Beta2 - Found in smooth muscle and enables blood vessels relaxation, uterine relaxation, and bronchodilator.
3) Beta3 - Found in adipose tissue and produces metabolic effects and also found in kidneys.
Chronotropic vs. Inotropic vs. Dromotropic drugs?
The difference is that inotropic is a cardiac drug that affects cardiac contraction, chronotropic is a cardiac drug that affects heart rate whereas dromotropic is a cardiac drug that affects conducting tissues of the heart.
Which Beta-adrenergic receptors are excitatory and which is inhibitory?
1) Beta1 - Excitatory
2) Beta2 - Inhibitory
Down-regulation vs. Up-regulation?
1) Down-regulation - When receptors are destroyed due to repeated/chronic exposure to an agonist.
2) Up-regulation - When receptors are increased due to repeated/chronic exposure to an antagonist
Examples of Down-regulation and Up-regulation?
1) Down-regulation - CHF patients have constant, high sympathetic outflow which results in down-regulation of beta1 adrenergic receptors.
2) PTs who take Beta-blockers (receptors increase because of exposure to antagonist)
Why should patients who take Beta-Blockers NEVER abruptly discontinue their meds?
PTs who take Beta-blockers have increase Beta receptors because of exposure to the antagonist. Abrupt discontinuation of the med leaves the increased amount of Beta receptor to get binded by an agonist which will severely increase cardiac rate. This is because the process of down regulation take weeks to happen.
Where Are Alpha1 receptors located and what is the sympathetic effect there?
1) Arteries - Vasoconstriction
2) Veins - Vasoconstriction
3) Lungs - Decreased bronchial secretions
4) GI Tract - Contraction of sphincters
5) Urinary Bladder - Contraction of Trigone and sphincter
6) Uterus - Contraction of pregnant uterus
7) Eyes - Mydriasis or dilation (radial muscle contraction)
8) Liver - Glycogenolysis & Glucogenesis
9) Sex Organs - Ejaculation
10) Salivary Glands - Slight increase in Secretions
Where are Alpha2 receptors located and what is the sympathetic effect there?
1) GI Tract - Inhibits secretion
2) Pancreas - Inhibits insulin secretion
Where are Beta1 receptors located and what are there sympathetic effects there?
1) Heart - Increased HR, automaticity, and force of contraction
2) kidneys - Renin Secretion
Where are Beta3 receptors located and what are there sympathetic effects there?
1) Urinary Bladder - Relaxation of detrusor muscle
2) Liver - Glycogenolysis & Glucogenesis
Where are M2 receptors located and what are there parasympathetic effects there?
1) Heart - Decreased HR, automaticity, and force of contraction
2) GI Tract - Relaxation of sphincters
Where are M3 receptors located and what are there parasympathetic effects there?
1) Lungs - Bronchoconstriction and increased bronchial secretions
2) Urinary Bladder - Contraction of detrusor muscles and relaxation of trigone and sphincter
3) Eye - Miosis or constriction (sphincter muscle contraction), ciliary muscle contraction for near vision, increased lacrimal gland secretions
4) Sex Organs - Erection
5) Salivary Glands - Stimulates watery secretions
6) Sweat Glands - Generalized secretions
Where are Beta2 receptors located and what are there sympathetic effects there?
1) Arteries - Vasodilation
2) Veins - Vasodilation
3) Lungs - Bronchodilation
4) GI Tract - Decreased motility
5) Urinary Bladder - Relaxation of detrusor muscle
6) Uterus - Relaxation of pregnant and non-pregnant uterus
7) Eye - Ciliary muscle relaxation for far vision
8) Liver - Glycogenolysis and Glucogenesis
What is the 1st messenger for and NMDA receptor? in other words, what binds to the MDA receptor?
Glutamate
What are the 5 different 2nd messengers?
1) cAMP
2) cGMP
3) IP3
4) DAG
5) Ca+
What are the effectors for the following receptors:
1) Alpha1
2) Alpha2
3) Beta1
4) Beta
5) M1, M3, M5
6) M2, M4
1) Alpha1 - Stimulates Phospholipase C
2) Alpha2 - Inhibits Adenalate Cyclase
3) Beta1 - Stimulates Adenalate Cyclase
4) Beta2 - Stimulates Adenalate Cyclase
5) M1, M3, M5 - Stimulates Phospholipase C
6) M2, M4 - Inhibits Adenalate Cyclase
What are the 2nd messengers for the following receptors:
1) Alpha1
2) Alpha2
3) Beta1
4) Beta
5) M1, M3, M5
6) M2, M4
1) Alpha1 - IP3, DAG, Ca2+
2) Alpha2 - cAMP
3) Beta1 - cAMP
4) Beta - cAMP
5) M1, M3, M5 - IP3, DAG, Ca2+
6) M2, M4 - cAMP
Which enzymes metabolizes cAMP?
Phosphodiesterase III metabolizes cAMP into AMP
(T/F?) Hypermagnesemia decreases the release of aCH from the presynaptic nerve?
True
Stimulation of which receptor results in a trancellular potassium shift?
Beta2 - this explains why drugs like albuterol cause hypokalemia
Why are drugs such as Atropine, Ephedrine and glycopyrolate ineffective on a transplanted heart?
Because a transplanted heart is severed from the ANS and is not under the influence of the vagus nerve or cardiac accelerator fibers. Direct acting agents such as isopreternol, glucagon and epi have to be used instead.
