Autonomic nervous system Flashcards
What are the 4 classifications of receptors?
A receptor receives the signal and instructs the cell to perform a specific function. Signal transduction is the process by which a cell converts this extracellular signal into an intracellular response.
Receptor classifications:
* Ion channel
* G-protein
* Enzyme-linked receptor
* Intracellular receptor
Describe the general architecture of the G protein second messenger system.
This is one area where it’s easy to get lost in the details. Your life will be easier if you understand the general architecture of the G protein system BEFORE trying to memorize the specifics about each receptor.
* 1st messenger (extracellular signal)
* Receptor (responds to the extracellular signal)
* G protein ( turns on or turns off an effector)
* Effector (activates or inhibits the second messenger)
* Enzymatic cascade ( a bunch of steps you don’t have to worry about)
* Cellular response (causes a physiologic change)
Remember that second messengers are tissue specific. For example, cAMP may cause a response in one cell type while causing a different response in a different cell type.
What second messenger system is associated with the alpha-1 receptor? what other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway:
* Histamine-1
* Muscarinic-1
* muscarinic-3
* Muscarinic-5
* Vasopressin-1 (vascular)
What second messenger system is associated with the alpha-2 receptor? What other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway.
* Muscarinic-2
* Dopamine-2 (presynaptic)
what second messenger system is associated with the beta-1 AND beta -2 receptor? What other receptors share a similar pathway?
Other receptors that share a similar 2nd messenger pathway:
* Histamine-2
* Vasopressin-2 (renal)
* Dopamine (postsynaptic)
Describe the autonomic innervation of the heart.
Heart:
Myocardium: Beta 1
conduction system: Beta 1
-> increased contractility, heart rate, conduction speed
-> M2-> Decreased contractility, heart rate and Conduction velocity
SNS: The cardiac accelerator fibers arise from T1-T4
PNS: Vagus nerve (CN X)
Describe the autonomic innervation of the vasculature
Vasculature
Arteries: a1>a2 : Vasoconstriction
Veins: a2>a1 : Vasoconstriction
Specific vascular beds
Myocardium : B2 : vasodilation
Skeletal muscle B2: Vasodilation
Renal: DA : Vasodilation
Mesenteric: DA: Vasodilation
Describe the autonomic innervation of the bronchial tree.
Beta-2 receptors are not innervated. Instead, they respond to catecholamines in the systemic circulation or in the airway (inhaled)
Describe the autonomic innervation of the kidney
Renal tubules: a2: diuresis (ADH inhibition)
Renin release: B1 : increased renin release
Describe the autonomic innervation of the eye.
Sphincter muscle (iris): -: -: M: Contraction (miosis)
Radial muscle (iris): a1: Contraction (mydriasis): -: -
Ciliary muscle: B2: relaxation (far vision): M: contraction (near vision)
Describe the autonomic innervation of the GI tract
Describe the autonomic innervation of the pancreas
Islet (beta cells): Alpha 2: Decrease insulin release
Beta 2: Increase insulin release
Describe the autonomic innervation of the bladder
Trigone & Sphincter: Alpha 1: contraction: M: Relaxation
Detrusor: Beta 2: Relaxation: M: contraction
List the steps of norepinephrine synthesis. What is the rate limiting step?
Norepinephrine is the primary neurotransmitter in the sympathetic nervous system.
Notice how and where EPI is synthesized
what are the 3 ways that NE can be removed from the synaptic cleft? Which is the most important?
NE is removed from the synaptic cleft in 1 of 3 way:
* Reuptake into the presynaptic neuron (accounts for 80%)
* Diffusion away from the synaptic cleft
* Reuptake by extraneural tissue
What enzymes metabolize NE and EPI? what is the final metabolic byproduct?
There are 2 metabolic pathways for norepinephrine and epinephrine
* Monoamine oxidase (MAO)
* Catechol-O-methyltransferase (COMT)
the final byproduct of NE and EPI metabolism is vanillylmandelic acid (VMA). Another name for this compound is 3-mthoxy-4-hydroxymandelic acid. An elevated level of VMA in the urine aids in the diagnosis of pheochromocytoma
List the 3 types of cholinergic receptors. Where are each of these found inside the body?
Nicotinic Type M (muscle):
* Neuromuscular junction
Nicotinic Type N (nerve):
* Preganglionic fibers at autonomic ganglia (SNS & PNS)
* Central nervous system
Muscarinic:
*Postganglionic PNS fibers at effector organs
* Central nervous system
Describe the synthesis, release, and metabolism of acetylcholine.
list the 5 components of the autonomic reflex arc
sensor -> afferent pathway -> control center-> efferent pathway -> effector
compare and contrast the architecture of the SNS and PNS efferent pathways
Both Pathways contain a pre- and postganglionic nerve fiber
PNS:
* Preganglionic: Long, myelinated, B-fiber, releases Ach
* Post-ganglionic: Short, unmyelinated, C-Fiber, release Ach
SNS:
* Preganglionic: Short, myelinated, B-Fiber, releases Ach
* Postganglionic: Long unmyelinated, C-fiber, releases NE (*Ach is released at sweat glands, piloerector muscles, and some vessels)
what is the origin of the efferent SNS pathways?
Thoracolumbar:
*T1-L3
* Cell bodies arise from the intermediolateral region of the spinal cord and axons exit via the ventral nerve roots
* Preganglionic fibers usually synapse with postganglionic fibers in the 22 paired sympathetic ganglia (mass effect)
what is the origin of the efferent PNS pathways?
Craniosacral:
* CN 3,7,9,10
* S2-S4
* preganglionic fibers synapse with postganglionic fivers near or in each effector organ (precise control of each organ)
Describe the innervation of the adrenal medulla. How is it different then the typical SNS efferent architecture?
The innervation of the adrenal medulla is unique; there are no postganglionic fibers.
The preganglionic fibers release Ach onto the chromaffin cells, and the chromaffin cells release EPI and NE into the systemic circulation at a ratio of 80% and 20% respectively
You can think of the adrenal medulla as an autonomic ganglion that is in direct communication with bloodstream
Describe the hemodynamic management of the pt with pheochromocytoma.
Understanding the hemodynamic management of this pt is critical to the success of your anesthetic. You must alpha block before you beta block! just remember that A comes before B.
Commonly used alpha antagonists include:
*Non-selective: phenoxybenzamine and phentolamine
* alpha-1 selective: Doxazosin and prazosin
Problems that arise from blocking the beta receptor first:
* Beta-2 blockade inhibits skeletal muscle vasodilation and increases SVR
* Beta-1 blockade reduces inotropy and can precipitate CHF in the setting of increased SVR.
what is the transcellular potassium shift, and what causes it to occur?
The transcellular K+ shift describes a number of processes that alter serum K+ by shifting K+ into or out of the cells
- Things that shift K+ into cells (ICF) leads to hypokalemia
- Things that shift K+ into the ECF lead to hyperkalemia
K shift in: Alkalosis, beta-2 agonists, theophylline, insulin
K shift out of cell: acidosis, cell lysis, hyperosmolarity, succinylcholine
Describe the anatomy and physiology of the baroreceptor reflex.
the baroreceptor reflex regulates short term blood pressure control.
* When the blood pressure rises, the baroreceptor reflex decreases heart rate, contractility, and systemic vascular resistance
* When blood pressure falls, the baroreceptor reflex increases heart rate, contractility, and systemic vascular resistance
longer term pressure control is mediated by the RAAS and ADH.
describe the anatomy and physiology of the Bainbridge reflex.
The bainbridge reflex increases heart rate when venous return is too high. This is beneficial, because it minimizes venous congestion and promotes forward flow.
* Sensor: SA node, RV, pulmonary veins
* Afferent: Vagus
* Control: Vasomotor center in the medulla
* Efferent: vagus (inhibition)
* Effector: SA node increases HR
Treatment: None required
Example: Autotransfusion during childbirth
describe the anatomy and physiology of the Bezold-Jarisch reflex.
The Bezold-Jarisch reflex decreases the heart rate when venous return is too low. This gives an empty heart adequate time to fill.
* Sensor: Cardiac mechanoreceptors (venous return) & cardiac chemoreceptors (ischemia)
* Afferent: Vagus
* Control: Vasomotor center in the medulla
* Efferent: Vagus
* Effector: SA node decreases heart rate & AV node decreases conduction velocity
Treatment: Restore preload (IVF and leg elevation) and increase heart rate (EPI is best)
Examples:
* Cardiac arrest during spinal anesthesia
* Massive hemorrhage
* Myocardial ischemia
*shoulder arthroscopy + interscalene block w/EPI + sitting position
describe the anatomy and physiology of the oculocardiac reflex
the oculocardiac reflex as the five (V) and dime (X) reflex
- Sensor: pressure on the eye or globe
- Afferent: Long and short ciliary n. -> ciliary ganglion -> opthalamic V1 of trigeminal n (CN V)-> gasserian ganglion
- Control: Vasomotor center in the medulla
- Efferent: Vagus
- Effectors: SA node decreases heart rate & AV node decreases conduction velocity
treatment:
* Ask the surgeon to remove the stimulus. This is usually enough to terminate the reflex
* Administer 100% oxygen, ensure proper ventilation, and deepen anesthetic
* Administer an anticholinergic (atropine or glyco)
Examples:
* Strabismus surgery
* Ocular trauma
* Retrobulbar block (Can cause or prevent the OCR)
what is the primary determinant of cardia output in the pt with a heart transplant? What is the consequence of this?
The transplanted heart is severed from autonomic influence, so the heart rate is determined by the intrinsic rate of the SA node. This explains why these pts often have a resting tachycardia (HR: 100-120 bpm)
If CO is the product of HR and SV ( and the heart rate is fixed), then CO becomes dependent on preload. Indeed, CO is highly dependent on cardiac filling. This feature makes these pts very sensitive to hypovolemia.
What drugs can be used to augment heart rate in the pt with a heart transplant?
Central to understanding this is knowing that there is no autonomic input from the cardiac accelerator (T1-4) or the vagus nerve.
- Drugs that directly stimulate the SA node can be used to increase HR (epi, isoproterenol, glucagon)
- Drugs that indirectly stimulate the SA node can NOT be used (atropine, glyco, and ephedrine)
A pt presents for removal of a glomus tumor. What are you primary concerns when planning your anesthetic?
Glomus tumors (glomangiomas) originate from neural crest cells. They tend to grow in the neuroendocrine tissues that lay in close proximity to the carotid artery, aorta, glossopharyngeal nerve, and the middle ear. These tumors usually aren’t malignant.
- They can release several vasoactive substances that can lead to exaggerated hyper- or hypotension (NE, 5-HT, histamine, bradykinin).
- Octreotide can be used to treat carcinoid-like s/sx.
- Cranial nerve dysfunction (glossopharyngeal, vagus, and hypoglossal) can cause swallowing impairment, aspiration of gastric contents, and airway obstruction.
- Surgical dissection of a glomus tumor that has invaded the internal jugular vein increases the risk of air embolism.
What are the anesthetic considerations for multiple system atrophy?
Multiple system atrophy (previously known as Shy-Drager syndrome) causes degeneration of the locus coeruleus, intermediolateral column of the spinal cord (where the cell bodies for the SNS efferent nerves live), and the peripheral autonomic nerves.
- Autonomic dysfunction (orthostatic hypotension)
- Treat HoTN with volume and direct acting sympathomimetics
- Exaggerated HTN response to ephedrine and possibly ketamine
Compare and contrast low, intermediate, and high dose epinephrine.
Low dose Epi (0.01-0.03 mcg/kg/min)
* at low doses, non-selective beta effects predominate. Beta-1 stimulation increases heart rate and contractility, while beta-2 stimulation mediates vasodilation in the skeletal muscle. The net effect is typically an increased CO with a reduction in blood pressure. Pulse pressure is increased (wider).
Intermediate dose epi (0.03-0.15 mcg/kg/min)
* This dose range is characterized by mixed beta and alpha effects
High dose epi (>0.15 mcg/kg/min):
* in this dose range, the alpha effects prevail and blood pressure rises. Supraventricular tachyarrhythmias are common, and these limit the usefulness of high dose EPI.
Describe the cardiovascular effects of isoproterenol
Isoproterenol is a synthetic catecholamine that stimulates beta 1 and beta 2 receptors
- it increases heart rate, contractility, and myocardial oxygen consumption
- It decreases SVR, which reduces diastolic BP. This may reduce coronary perfusion pressure (CP= AoDB-LVEDP)
- It causes severe dysrhythmias and tachycardia
- IT vasodilates nonessential vascular beds, such as those in the muscle and skin. This characteristic precludes its use in septic shock.
list 4 clinical indications for isoproterenol.
- Chemical pacemaker for bradycardia unresponsive to atropine.
- Heart transplant
- Bronchoconstriction
- Cor pulmonale
in what situations should ephedrine NOT be use to treat hypotension?
Uses endogenous catecholamine stores from the presynaptic sympathetic nerve. Multiple doses can cause tachyphylaxis (Progressively smaller response to a given dose after multiple administrations)
* Ephedrine doesn’t work well when neuronal catecholamine stores are depleted (sepsis) or absent (heart transplant)
* Risk of hypertensive crisis in pts on MAO inhibitors
* Conditions where increased HR or contractility is detrimental to hemodynamics
How does vasopressin increase blood pressure?
Vasopressin restores blood pressure in two ways:
* V1 receptor stimulation causes intense vasoconstriction
* V2 receptor stimulation increases intravascular volume by stimulating the synthesis and insertion of aquaporins into the walls of the collecting ducts. This increases water (but not solute) reabsorption and lowers serum osmolarity
Aldosterone increases water and sodium reabsorption (serum osmolarity is unchanged). This is an important difference between vasopressin and aldosterone
what is the best treatment for vasoplegic syndrome?
Refractory HoTN is also called vasoplegic syndrome. The key here is that hypotension does not respond to conventional therapies such as adrenergic agonists, hydration, and reducing depth of anesthesia.
- Vasopressin is the best treatment (0.5-1 unit IV bolus followed by an infusion of 0.03 units/min)
- the incidence of vasoplegic syndrome is increased by ACE inhibitors or angiotensin receptor antagonists
- Methylene blue is the next best choice
the 6 drugs that are selective for the beta 1 receptor
these drugs are beta-1 selective
* Atenolol
* Acebutolol
* Betaxolol
* Bisoprolol
* Esmolol
* Metoprolol
Knowing what you know about the beta-1 and beta-2 receptor, you should be able to predict their side effects
A’s B’s E, beginning of alphabet plus M
list 6 non-selective beta antagonists
they antagonize beta 1 and beta 2 receptors
* Carvedilol
* Labetolol
* Nadolol
*Pindolol
* Propranolol
* Timolol
Knowing which receptors they target you can predict their side effects
Lower alphabet plus C
what is the primary site of metabolism of the commonly used beta blockers? What are 2 exceptions?
Most beta blockers depend on the liver as their primary site of metabolism. Examples include: propranolol, metoprolol, labetalol, and carvedilol.
There are 2 exceptions:
* Esmolol is metabolized by RBC esterases (not pseudocholinesterase)
* Atenolol is eliminated by the kidneys (caution in renal failure)
which beta blockers have local anesthetic properties? what is another name for this?
Membrane stabilizing properties is another way of saying that a drug has local anesthetic-like effects.
This effect reduces the rate of rise of the cardiac action potential, however it probably only occurs when these drugs reach toxic levels. Examples include:
* propranolol
* acebutolol
what is intrinsic sympathomimetic activity? which drugs exert this effect?
Beta blockers that exert a partial agonist effect, while simultaneously blocking other agonists that have a higher affinity for the beta receptor are said to have intrinsic sympathomimetic activity.
- Examples: labetalol and pindolol
