Unit 2: ANS Flashcards
What are the four classifications of receptors?
- Ion channel
- G protein coupled receptor
- Enzyme linked receptor
- Intracellular receptor
- receptor receives the signal and instructs the cell to perform a specific function
- signal transduction = cell converts this extracellular signal into an intracellular response
What is the general architecture of the G protein second messenger system?
- 1st messenger (extracellular signal)
- Receptor (responds to extracellular signal)
- G protein (turns on or off an effector)
- Effector (activates or inhibits 2nd messenger)
- 2nd messenger (primary intracellular signal)
- Enzymatic cascade
- Cellular response (causes physiologic change)
*2nd messengers are tissue specific
What 2nd messenger system is associated with the alpha-1 receptor? What other receptors share a similar pathway?
Alpha-1 Gq -> stimulates Phospholipase C production -> IP3, Calcium, DAG
Others that share similar pathway:
- Histamine-1
- Muscarinic-1
- Muscarinic-3
- Muscarinic-5
- Vasopressin-1 (vascular)
What 2nd messenger system is associated with the alpha-2 receptor? What other receptors share a similar pathway?
Alpha-2 Gi -> inhibits Adenylate Cyclase -> ATP, cAMP
Others that share similar pathway:
- Muscarinic-2
- Dopamine-2 (presynaptic)
What 2nd messenger system is associated with the beta-1 AND beta-2 receptor? What other receptors share a similar pathway?
Beta-1 and Beta-2 Gs -> stimulate Adenylate Cyclase -> ATP, cAMP
Others that share similar pathway:
- Histamine-2
- Vasopressin-2 (renal)
- Dopamine-1 (postsynaptic)
Describe the autonomic innervation of the heart
SNS: cardiac accelerator fibers arise from T1-T4
PNS: vagus nerve
Myocardium: beta-1 increases contractility – M2 decreases contractility
Conduction System: beta-1 increases HR and conduction speed – M2 decreases HR and CV
Describe the autonomic innervation of the vasculature
- Arteries: alpha-1 > alpha-2 –> vasoconstriction
- Veins: alpha-2 > alpha-1 –> vasoconstriction
- Myocardium: beta-2 –> vasodilation
- Skeletal muscle: beta-2 –> vasodilation
- Renal: dopamine –> vasodilation
- Mesenteric: dopamine –> 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: alpha-2 –> diuresis (ADH inhibition)
Renin Release: beta-1 –> increased renin release
Describe the autonomic innervation of the eye
Sphincter Muscle (iris): muscarinic –> contraction (miosis)
Radical Muscle (iris): alpha-1 –> contraction (mydriasis)
Ciliary Muscle: beta-2 –> relaxation (far vision) – muscarinic –> contraction (near vision)
Describe the autonomic innervation of the GI tract
Sphincters: alpha-1 –> contraction – muscarinic –> relaxation
Motility & Tone: alpha-1, alpha-2, beta-1, beta-2 –> decreases – muscarinic –> increases
Salivary Glands: alpha-2 –> decreases – muscarinic –> increases
Gallbladder & Ducts: beta-2 –> relaxation – muscarinic –> contraction
Describe the autonomic innervation of the pancreas
Islet (beta cells):
- alpha-2 –> decreases insulin release
- beta-2 –> increases insulin release
Describe the autonomic innervation of the bladder
Trigone & Sphincter:
- alpha-1 –> contraction
- muscarinic –> relaxation
Detrusor:
- beta-2 –> relaxation
- muscarinic –> contraction
What are the steps of norepinephrine synthesis? What is the rate limiting step?
- Tyrosine –> DOPA via Tyrosine Hydroxylase (rate limiting step)
- DOPA –> Dopamine via DOPA decarboxylase
- Dopamine –> Norepinephrine via Dopamine B-hydroxylase
*norepi –> epi via phenylethanolamine N-methyltransferase in the adrenal medulla
What are the three ways that Norepi can be removed from the synaptic cleft? Which is the most important?
- Reuptake into presynaptic neuron (accounts for 80%)
- Diffusion away from synaptic cleft
- Reuptake by extraneural tissue
What enzymes metabolize Norepi and Epi? What is the final metabolic byproduct?
- Monoamine Oxidase (MAO)
- Catechol-O-methyltransferase (COMT)
-final byproduct = vanillylmandelic acid (VMA)
What are the three types of cholinergic receptors? Where are each found in the body?
1.Nicotinic Type M (muscle):
- neuromuscular junction
2.Nicotinic Type N (nerve):
- preganglionic fibers at autonomic ganglia (SNS & PNS)
- CNS
3.Muscarinic:
- postganglionic PNS fibers at effector organs
- CNS (M1,3,5 activates Phospholipase C; M2,4 inhibits Adenylyl Cyclase)
** Nicotinic = ion channel
** Muscarinic = G-protein coupled
How is Acetylcholine synthesized, released, and metabolized?
Synthesized in pre-synaptic nerve terminal – Acetyl Coenzyme A + Choline –(ChAT)–> Acetylchoine + Coenzyme A + H2O
Released after an action potential acts on the preganglionic neuron
Metabolized by Acetylcholinesterase into Acetate and Choline
What are the five components of the autonomic reflex arc?
Sensor –> Afferent Pathway –> Control Center –> Efferent Pathway –> Effector
What type of nerve fibers make up the PNS and SNS?
PNS:
- preganglionic = long, myelinated B-fibers – releases ACh
- postganglionic = short, unmyelinated C-fibers – releases ACh
SNS:
- preganglionic = short, myelinated B-fibers – releases ACh
- postganglionic = long, unmyelinated C-fibers – 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 fibers near or in each effector organ (precise control of each organ)
How is the innervation of the adrenal medulla different than the typical SNS efferent architecture?
There are no postganglionic fibers
- preganglionic fibers release ACh onto the chromaffin cells, which release Epi (80%) and NE (20%) into systemic circulation
- adrenal medulla = autonomic ganglion that is in direct communication w/ the bloodstream
Describe the hemodynamic management of a pt with pheochromocytoma
Must alpha block BEFORE beta block
Alpha Antagonists:
- Phenoxybenzamine and Phentolamine (non-selective)
- Doxazosin and Prazosin (alpha-1 selective)
What is the transcellular potassium shift? What causes it to occur?
It describes a number of processes that alter serum K+ by shifting K+ into or out of cells
- K+ Shift In: alkalosis, beta-2 agonists, theophylline, insulin
- K+ Shift Out: acidosis, cell lysis, hyperosmolarity, SUX
What is the Baroreceptor reflex?
Regulates short term BP control
- when BP rises, baroreceptor reflex decreases HR, contractility, and SVR
- when BP falls, baroreceptor reflex increases HR, contractility, and SVR
What is the Bainbridge reflex?
Increases HR when venous return is too high – minimizes venous congestion and promotes forward flow
- Sensor = SA node, RV, Pulmonary veins
- Afferent = Vagus
- Control Center = Vasomotor center in the medulla
- Efferent = Vagus (inhibition)
- Effector = SA node increases HR
*ex: Autotransfusion during childbirth
What is the Bezold-Jarisch reflex?
Decreases HR when venous return is too low – gives an empty heart adequate time to fill
- Sensor = Cardiac mechanoreceptors (venous return) and Cardiac chemoreceptors (ischemia)
- Afferent = Vagus
- Control Center = Vasomotor center in medulla
- Efferent = Vagus
- Effector = SA node decreases HR and AV node decreases conduction velocity
Treatment = restore preload (IVF) and increased HR (Epi)
*ex: cardiac arrest during spinal, massive hemorrhage, MI, shoulder arthroscopy + interscalene block w/ Epi + sitting position
What is the pathway of the Oculocardiac reflex?
“Five and Dime”
- Sensor = Pressure to the eye or globe
- Afferent = Long and short ciliary n. –> ciliary ganglion –> ophthalmic division V1 of trigeminal n. –> gasserian ganglion
- Control Center = Vasomotor center in the medulla
- Efferent = Vagus
- Effector = SA node decreases HR and AV node decreases conduction velocity
*ex: strabismus surgery, ocular trauma, retrobulbar block
What is the primary determinant of CO in a pt w/ a heart transplant? What is the consequence of this?
- Transplanted heart has fixed HR so CO is dependent on Preload
- transplanted heart is severed from autonomic influence – HR is determined by intrinsic rate of SA node (HR typically 100-120)
-Patient is very sensitive to hypovolemia
What drugs can be used to augment HR in a heart transplant pt?
Drugs that directly stimulate the SA node CAN be used to increase HR: Epinephrine, Isoproterenol, Glucagon
Drugs that indirectly stimulate the SA node CANNOT be used: Atropine, Glycopyrrolate, and Ephedrine
*there is no autonomic input from the cardiac accelerator fibers (T1-T4) or vagus nerve
What are the primary anesthetic concerns for removal of a glomus tumor?
Glomus tumors originate from neural crest cells and tend to grow in neuroendocrine tissues that lay close proximity to carotid artery, aorta, glossopharyngeal n. and middle ear
- Can release several vasoactive substances that can lead to exaggerated HTN or HoTN
- Octreotide can be used to treat carcinoid like s/sx
- Cranial n. dysfunction (glossopharyngeal, vagus, hypoglossal) can cause swallowing impairment, aspiration, and airway obstruction
- Surgical dissection of tumor that invaded IJ vein = risk of air embolism
What are the anesthetic considerations for multiple system atrophy? What is another name for it?
Also known as Shy-Drager Syndrome
Causes degeneration of the locus coeruleus, IML column of spinal cord, and peripheral autonomic nerves
- autonomic dysfunction – orthostatic HoTN
- treat HoTN w/ 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
- non-selective beta effects predominate
- beta-1 stimulation increases HR and contractility, while eta-2 mediates vasodilation in skeletal muscle = net effect of increased CO w/ reduction in SVR
INTERMEDIATE dose Epi: 0.03-0.15 mcg/kg/min
-mixed beta and alpha effects
HIGH dose Epi: > 0.15 mcg/kg/min
- alpha effects dominate and BP rises
- supraventricular tachyarrhythmias are common – limit the usefulness of high dose epi
What are the CV effects of isoproterenol?
it is a synthetic catecholamine that stimulates beta-1 and beta-2
- increases HR, contractility, and myocardial oxygen consumption
- decreases SVR (reduces DBP) – may reduce CPP
- causes severe dysrhythmias and tachycardia
- vasodilates nonessential vascular beds (i.e. in the muscle and skin) – precludes its use in septic shock
What are the four clinical indications for isoproterenol?
- Chemical pacemaker for bradycardia unresponsive to atropine
- Heart transplant
- Bronchoconstriction
- Cor pulmonale
In what situations should ephedrine NOT be used to treat hypotension?
- Doesn’t work well when neuronal catecholamine stores are depleted (sepsis) or absent (heart transplant)
- Pt is on MAO inhibitors – risk of hypertensive crisis
- Conditions where increased HR or contractility is detrimental to hemodynamics
How does vasopressin increase BP?
V1 receptor stimulation: causes intense vasoconstriction
V2 receptor stimulation: increases intravascular volume by stimulating synthesis and insertion of aquaporins into the walls of collecting ducts – increases water (but not solute) reabsorption and lowers serum osmolarity
What is vasoplegic syndrome? What is the best treatment?
Also known as Refractory Hypotension
- hypotension doesn’t respond to conventional therapies such as adrenergic agonists, hydration, and reducing depth of anesthesia
- incidence is increased by ACE inhibitors or ARBs
Vasopressin (0.5-1 unit IV bolus followed by an infusion of 0.03 units/min) = best treatment
Methylene blue = next best choice
What six drugs are beta-1 selective?
- Atenolol
- Acebutolol
- Betaxolol
- Bisoprolol
- Esmolol
- Metoprolol
What six drugs are non-selective beta antagonists?
- Carvedilol
- Labetalol
- Nadolol
- Pindolol
- Propranolol
- Ttimolol
What is the primary site of metabolism of the commonly used beta blockers? What are two exceptions?
Dependent on LIVER as primary site of metabolism
-propranolol, metoprolol, labetalol, carvedilol
Exceptions = Esmolol (metabolized by RBC esterases) and Atenolol (metabolized by kidneys)
What beta blockers have local anesthetic properties? What is another name for this?
Propranolol and Acebutolol
-effect reduces the rate of rise of the cardiac action potential (only occurs when reach toxic levels)
Also known as Membrane stabilizing properties
What is intrinsic sympathomimetic activity? Which drugs exert this effect?
Intrinsic Sympathomimetic Activity = Beta blockers that exert a partial agonist effect, while simultaneously blocking other agonists that have a higher affinity for beta receptor
ex: Labetalol and Pindolol
What are three alpha antagonists? What is the MOA for each?
Alpha antagonists reduce BP by causing vasodilation (decreased SVR)
- Phenoxybenzamine: long acting, non-selective, noncompetitive antagonist of alpha-1 and alpha-2
- Phentolamine: short acting, non-selective, competitive antagonist of alpha-1 and alpha-2
- Prazosin: alpha-1 selective antagonist
