Autonomic Nervous System Physiology Flashcards
Genral motor of SNS:
1) Motor output of the sympathetic nervous system descends from the brain OR input from afferents (from the body) synapses on neurons in the intermediolateral cell column (gray matter)
-Located from T1-L3
2) SNS neurons send efferent axons through the white rami communicants to a paravertebral ganglion
3) Within the paravertebral ganglion, the axon can:
-synapse within the paravertebral ganglion at the spinal level
-Continue to another paravertebral ganglion at a different spinal level and synapse there
-Pass through the paravertebral ganglion and continue to a prevertebral ganglion (through a splanchnic nerve) and synapse there
Solid lines= efferents from spinal cord to first ganglion
-pre-ganglionic fibre
Dotted lines=efferents from ganglion to target organ
-post-ganglionic fibre
Intermediolateral horn/column:
-Found in lamina VII of the thoracic and upper lumbar spinal cord.
The descending pathways that influence neurons in this column are diffuse and hard to distinguish.
-Reflex pathways from afferents also impact the activity of neurons in this column
Basic SNS anatomy- “option 1”
Neuron in the intermediolateral horn (pre-ganglionic neuron) => synapses on a neuron in the paravertebral ganglion at that same spinal level
-Axon travels through the white rami comminicantes, synapses on the post ganglionic neuron
-White rami communicantes are myelinated
The postganglionic neuron sends efferents out to visceral organs.
-Gray rami communicantes (unmyelinated fibres) join the spinal nerve
Option 1 model is a typical:
sympathetic input to skin, blood vessels at the spinal level
Also some of the inputs to the heart and lungs
Basic SNS Anatomy “option 2”
Neuron in the intermediolateral horn (pre-ganglionic neuron) => synapses on a neuron in a paravertebral ganglion at a different spinal level.
Cervical ganglia- receive fibres from the upper thoracic intermediolateral horn:
-Superior cervical ganglion: around the level of C1-C4
-Middle cervical ganglion: C5-C6
-Inferior cervical ganglion: C7-C8
The inferior cervical ganglion fuses with the fibres from the first thoracic ganglion to form the stellate ganglion
Superior cervcial ganglion:
SNS input to the cranial nerves
-Nerves travel along blood vessels and often join the parasympathetic fibres of cranial nerves
(CN III, VII, IX, X)
Middle + stellate: SNS input to:
-heart
-trachea bronchi, bronchioles
The heart and lungs receive inputs from “option 1” and “option 2” gray ramii:
forms web-like cardiac and pulmonary plexuses that innervate these structures
Long ciliary nerves =>
SNS input to pupil:
-pupillary dilation
-accompany short ciliary nerves (CN III)
SNS input tends to make tears, saliva less “watery” more “mucus-y”:
-The SNS inputs tend to accompany the cranial nerves at some point along their course.
-CN VII, IX
Basic SNS Anatomy “Option 3”
Neuron in the intermediolateral horn => passes through the paravertebral ganglion (no synapse) => synapses on a pre-vertebral ganglion
The white ramii form nerves on the way to the prevertebral ganglion.
Greater splanchnic nerve =>
celiac ganglion (T5-T9)
Lesser splanchnic nerve =>
superior mesenteric ganglia, aorticorenal ganglia (T10-T11)
Least splanchnic nerve =>
renal plexus/ganglia (T12)
Lumbar & sacral splanchnic nerves =>
inferior mesenteric ganglia, plexuses to pelvic and lower abdominal organs (L1-L2)
Sympathetic nervous system
Sympathetic nervous system:
-Short pre-ganglionic fibres, longer post-ganglionic fibres
-Neuronal cell bodies in the intermediolateral horn of T1-L2
-Ganglia can be paravertebral or prevertebral
-Preganglionic fibres can be white rami communicantes from the spinal cord or splanchnic nerves
Parasympathetic nervous system:
-Long pre-gaglionic fibrs, short post-ganglionic fibres
-Neuronal cell bodies in the brainstem (cranial nerve nuclei) or sacral spinal levels
-No prevertebral or post vertebral ganglia
Basic PaNS anatomy:
Cranial parasympathetic nervous system:
Pupillary constriction (CN III):
Edinger-westphal mucleus (midbrain) => ciliary ganglion
Lacrimal gland, nasal mucous secretins (CN VII):
superior salivatory nucleus (pons) => sphenopalatine ganglion
Sublingual, submaxillary salivary glands (CN VII):
Superior salivatory nucleus (pons) => submandibular ganglion
Parotid salivary glands (CN IX):
Inferior salivatory nucleus (medulla) => otic ganglion
Salivary & lacrimal secretion is mainly under parasympathetic nervous system control:
PaNS => more saliva, more watery, more digestive enzymes
SNS => less fluid, more “sticky”
PaNS: The vagus:
Responsible for most parasympathetic output:
-nucleus: dorsal motor nucleus of the vagus
-Longest course of any cranial nerve: leaves through jugular foramen and descends alongside the carotid arteries
-Forms anterior and posterior trunks at the stomach and divides to supply plexuses in the abdominal cavity, all the way to the left (distal) colon
PaNS: Sacral Efferents:
Bodies found in S2-S4 levels
-Travel with pelvic splanchnic nerves to supply:
-the rectum
-Bladder
-male and female reproductive organs
Neurotransmitters:
Sympathetic nervous system:
“fight or flight”
-Increases heart rate and cardiac output
-Improves ventilation
-Decreases digestive function
-Increases glucose availability (gluconeogenesis, glycogenolysis)
-Increases blood flow to skeletal muscles, heart
-Decreases blood flow to GI tract, skin, kidney’s
-Reduced contraction of bladder, contraction of urethral sphincter
-Major neurotransmitters: epinephrine & norepinephrine
The sympathetic nervous system tends to supply _____ and ______ organs
Visceral & non-visceral:
-Skin (blood vessels, glands)
-Skeletal muscles (blood vessels, general metabolism)
Parasympathetic nervous system:
“rest ad digest”
-decreases heart rate and cardiac output
-Bronchoconstriction and increased mucous secretion
-Increases digestive function and GI motility
-Increases blood flow to digestive tract
-Increased bladder contraction, relaxation of urethral sphincter
-Increased blood flow to external genilatlia
-Major neurotransmitter: Acetylcholine
The parasympathetic nervous system has relatively little impact on blood vessels outside of:
-the GI system
-the reproductive system
Acetylcholine metabolism:
Acetylcholine is synthesized in presynaptic nerve terminals and then stored in vesicles.
Reaction:
Acetyl-CoA + choline => acetylcholine
Enzyme: choline acetyltransferase
After it’s secreted into the synapse, it’d degraded by acetylcholinesterase.
-Degraded to acetate and choline (choline is taken back up into the presynaptic terminal)
Basic cholinergic synapse:
Acetylcholinesterase is widely distributed in connective tissue throughout the body and in the synapse of cholinergic terminals.
Catecholamine synthesis:
Norepinephrine synthesis is slightly more complicated:
-Outside the vesicle:
tyrosine => Dopa (hydroxylation)
Dopa => Dopamine (decarboxylation)
Then, dopamine is transported into the synaptic vesicle:
Dopamine => norepinephrine (hydroxylation)
In the adrenal medulla, most norepinephrine is converted into epinephrine through methylation (in the vesicle)
Norepinephrine => epinephrine (methylation)
Catecholamine degradation:
50-80% of secreted norepinephrine is taken up again into the presynaptic terminal.
-not an option for epinephrine, which is secreted into the bloodstream by the adrenal medulla (endocrine)
Norepinephrine can be broken down by monoamine oxidase near the synapse.
-degradation product-dihydromandelic acid (FYI)
It can also be broken down by catechol-O-methyl-transferase (COMT)
-COMT is widely distributed throughout tissues
-Degradation product is metanephrine (FYI)
Major types of receptors:
Study chart:
Eye:
-Both parasympathetic (constriction) and sympathetic (dilation) outputs are important for pupillary size
-However, focusing the lens is mostly under control of the parasympathetic nervous system
Nasal, lacrimal, salivary, gastrointestinal glands:
-Strongly stimulated by parasympathetic activity-lots of watery secretions that are rich in enzymes (when enzymes apply)
-Glandular secretion can also be stimulated by the SNS-less watery, therefore usually lower rate of secretion
-The glands of the intestines are less controlled by the ANS, more by the food in the lumen of the gut
Sweat glands:
stimulated by the sympathetic nervous system-however, the neurotransmitter secreted is acetylcholine
Blood vessels:
Sympathetic nervous system: vasoconstriction in most vascular beds-mediated by alpha-1 receptors:
-Vasodilation in others mediated by beta-2 receptors in skeletal muscles, heart, liver
Parasympathetic nervous system: very limited effect on any blood vessels outside the GI tract and reproductive organs
Heart:
Sympathetic nervous syetm: beta -1 receptors increase contractility (basically, force of contraction) and heart rate => increased cardiac output
Parasympathetic: muscarinic receptors decrease heart rate but have a small (negative) influence on contractility
Glucose metabolism:
No role for the parasympathetic nervous system.
Gluconeogenesis, glycogenolysis, hyperglycemia with sympathetic nervous system stimulation.
The sympathetic nervous system can participate in specific, localized responses as well:
the usual day to day function of the SNS
The SNS can also be overwhelmingly activated (mass discharge) to accomplish the “fight or flight” response:
Arterial pressure, heart rate, and perfusion to skeletal muscle, heart, brain increase
Decreased blood flow through the GI tract, skin, kidney’s
Hyperglycemia, increased general cellular metabolism, and increased coagulation
Baroreceptor reflex:
Afferent: baroreceptors from CNs IX, and X
Efferent: parasympathetic and sympathetic => CN X, thoracic plexus
GI reflexes mediated by sensing food (whether sight/taste/smell or presence of food/secretions in the lumen)
Afferent: visceral receptors from CN X
Efferent: CN X
Micturition (urination) reflex:
Afferents & efferents at the level of the sacral spinal cord.
Nucleus tractus solitarius in the medulla receives input from the ________, sends output to a wide variety of other brain areas.
afferents
Adrenergic agonists:
Acting outside receptors
Acting directly at the receptors
Adrenergic antagonists:
Acting outside receptors
Acting directly at the receptor
Cholinergics:
Cholinomimetics
Anticholinergics
How could we increase activation of the catecholamine receptor on the post-synaptic membrane?
How could we decrease?
Increased catecholamine release: This can be achieved by increasing the firing rate of sympathetic neurons that release catecholamines, such as norepinephrine and epinephrine. This can be induced by stress, exercise, or other stimuli that activate the sympathetic nervous system.
Reduced reuptake of catecholamines: Catecholamines are normally reabsorbed back into presynaptic neurons by transporter proteins. Blocking these transporters can prevent the reuptake of catecholamines, increasing their concentration in the synaptic cleft and enhancing their ability to activate receptors. Drugs like cocaine and amphetamines are examples of reuptake inhibitors.
Desensitization of G proteins: G proteins are intermediaries between receptor activation and cellular responses. When receptors are repeatedly activated, they can become desensitized, meaning the G protein dissociates from the receptor less readily, reducing the overall signaling response. Blocking desensitization can prolong the activation of the receptor.
Upregulation of receptor expression: The number of catecholamine receptors on the postsynaptic membrane can fluctuate depending on various factors. Increasing receptor expression can lead to increased sensitivity to catecholamines. Drugs like beta-adrenergic agonists can induce receptor upregulation.
Decreasing activation
Reduced catecholamine release: This can be achieved by inhibiting sympathetic neuron activity or preventing the synthesis of catecholamines. Drugs like beta-adrenergic blockers and reserpine can reduce catecholamine release.
Enhanced reuptake of catecholamines: Increasing the activity of catecholamine transporter proteins can promote the reuptake of catecholamines from the synaptic cleft, reducing their concentration and diminishing their ability to activate receptors. Drugs like tricyclic antidepressants and monoamine oxidase inhibitors are examples of reuptake enhancers.
Internalization of receptors: When receptors are repeatedly activated, they can internalize, meaning they are internalized into the cell and removed from the postsynaptic membrane. This reduces the number of receptors available for activation. Drugs like glucocorticoids can induce receptor internalization.
Degradation of receptors: Catecholamine receptors are subject to degradation by enzymes like protein phosphatases. Increasing the activity of these enzymes can degrade receptors, reducing their number and sensitivity.
Downregulation of receptor expression: Chronic activation of catecholamine receptors can lead to downregulation, meaning the number of receptors on the postsynaptic membrane decreases. This can reduce the overall sensitivity to catecholamines.
Prevention of storage in the NT vesicle:
Reserpine-blocks VMAT => depletion of catecholamines
decrease catecholamine transmission
Non-vesicle mediated “leakage” of neurotransmitter from the presynaptic terminal:
Amphetamine, tyramine
Increase catecholamine transmission
Inhibition of reuptake at the presynaptic terminal:
Cocaine, selective norepinephrine reuptake inhibitors (Effexor)
Increase catecholamine transmission
Inhibition of NT degradation:
Mono-amine oxidase inhibitors (tranylcypromine)
Increase catecholamine transmission
Inhibition of NT release due to auto-receptor activation:
Clonidine thought to be a major example.
decrease catecholamine transmission
Agonists:
A substance that activates a receptor when it bonds to it.
Variation: a partial agonist is a substance that binds to a receptor but doesn’t activate it fully.
Antagonist:
a substance that inactivates a receptor or enzyme when it binds to it.
Can be reversible: it will eventually “let go” of the receptor or enzyme
Can be irreversible: it stays bound, and the receptor or enzyme (usually enzyme) is rendered useless
Receptor selectivity:
Alpha and beta receptors have different affinities for different agonists and antagonists.
For example: beta receptors have. high affinity for isoproterenol, but alpha receptors have a negligible affinity.
-Isoproterenol is therefore a selective beta-agonist
Beta-1 receptors have a high affinity for metoprolol, but beta-2 receptors don’t.
-Metoprolol is therefore a selective beta-1 antagonist
Phenylephrine:
Selective agonist for alpha-1 receptors
Main indication is as an over the counter decongestant.
- Causes vasoconstriction and decreased secretions from the nasal mucosa
Can also be used IV (emergently) to increase blood pressure
Clonidine:
Selective alpha-2 agonist
-Acts on presynaptic terminals to reduce adrenergic transmission in the central nervous system
Main indication is as an antihypertensive: reproduction of sympathetic nervous system activity
Isoproterenol and dobutamine are mostly used in internal medicine/intensive care settings:
Isoproterenol: activates beta-1 & beta-2 receptors
Dobutamine: activates beta-1 receptors with less beta-2 receptor effect.
Both increase cardiac output… but dobutamine will increase blood pressure the most.
Albuterol, salbutamol are inhaled selective beta-2 agonists:
activated beta-2 receptors in the bronchioles
