Unit 2 Autonomic Nervous System Flashcards
1
Q
List 3 forms of extracellular signals?
A
Chemical
Electrical
Mechanical
2
Q
What are the 4 classifications of receptors?
A
Ion channel
G-Protein Coupled Receptor
Enzyme Linked Receptor
Intracellular receptor
3
Q
Describe an ion channel
Example
A
An ion conducting pore that opens and closes to control ions flowing along their concentration gradient.
Voltage-gated sodium channel in the neuron
4
Q
What are the 2 ways a GPCR can work?
Example
A
- It opens or closes an ion channel
- It activates or inhibits an enzyme inside the cell
Alpha-1 receptor in vascular smooth muscle
5
Q
Describe an enzyme linked receptor.
Example
A
The receptor is also an enzyme
At rest the catalytic domain is inactive
When the signal binds the catalytic domain becomes activated
Insulin receptor in skeletal muscle (linked to tyrosine kinase)
6
Q
Describe an intracellular receptor.
Examples
A
A signal diffuses through the cell membrane and binds to the receptor located inside the cell.
Steroids bind to receptors in the cytoplasm
Thyroid hormone binds to receptors in the cell nucleus
7
Q
What is the general flow of events with a GPCR?
A
First messenger > GPCR > Effector > Second messenger > Cellular response
8
Q
What is a ligand (GPCR)?
A
The first messenger that binds to the GPCR. Can be endogenous or exogenous.
9
Q
Where is the GPCR?
A
In the cell membrane, making it accessible from outside the membrane
10
Q
How many subunits does the G-protein have?
A
3:
Alpha
Beta
Gamma
11
Q
What is the function of the protein on the GPCR?
A
The G-protein either stimulates or inhibits an effector (enzyme or channel)
12
Q
What are the G-proteins? What do each do?
A
Gs: stimulatory
Gq: stimulatory
Gi: inhibitory
13
Q
What happens with a ligand binds to the GPCR?
A
The ligand-receptor interaction activates the G-protein.
This causes the alpha subunit to dissociate from the beta and gamma subunits.
The alpha subunit of a Gs or Gq will turn on an effector, while the alpha subunit of a Gi protein will turn off an effector.
When the ligand unwinds from the receptor, the alpha subunit rejoins the beta and gamma subunits, and its interaction with the effector ends.
14
Q
What is the function of the effector (GPCR)?
A
To activate the second messenger
15
Q
Name 2 enzymatic effectors
A
Adenylate cyclase
Phopholipase C
16
Q
Name 2 ion channel effectors
A
GABA-A
M2 receptors at the SA node
17
Q
List the 5 second messengers
A
- Cyclic adenosine monophosphate (cAMP)
- Cyclic guanosine monophosphate (cGMP)
- Inositol triphosphate (IP3)
- Diacylglycerol (DAG)
- Calcium ion (Ca+2)
18
Q
Mnemonic for Gq GPCR?
A
Gq’s HAV 1 M&M Gq stimulates phospholipase C PLC turns on IP3, Ca+2, DAG Histamine 1 Alpha 1 Vasopressin 1 Muscarinic 1 Muscarinic 3 (apex also says 5)
19
Q
Mnemonic for Gi GPCR?
A
Gi MAD2 Gi inhibits adenylate cyclase Adenylate cyclase turns off ATP and cAMP Muscarinic 2 (apex also says 4) Alpha 2 Dopamine 2
20
Q
Mneumonic for Gs GPCR?
A
Gs does all the rest Gs stimulates adenylate cyclase Adenylate cyclase turns on ATP and cAMP Beta 1 and 2 Dopamine 1 Vasopressin 2 Histamine 2
21
Q
Nicotinic receptors are located where? What type of signal transduction?
A
ANS ganglia, NMJ, and CNS
Ion channels
22
Q
Which dopamine receptors are presynaptic and which are postsynaptic?
A
Pre: D2
Post: D1
23
Q
Which vasopressin receptors are in the vasculature and which are in the renal tubules?
A
Vasculature: V1
Renal tubules: V2
24
Q
ANS receptors and physiologic action of the heart? PNS?
A
SNS:
Myocardium B1
Conduction system B1
Increased contractility, HR, and conduction speed
The cardiac accelerator fibers arise from T1-T4
PNS: Myocardium M2 Conduction system M2 Decreased contractility, HR, conduction speed Vagus nerve CN X
25
ANS receptors and physiologic action of vasculature
SNS:
Arteries a1 > a2 -> vasoconstriction
Veins a2 > a1 -> vasoconstriction
PNS:
No parasympathetic receptors
26
```
ANS receptors and physiologic action of specific vascular beds:
Myocardium
Skeletal muscle
Renal
Mesenteric
```
Myocardium: B2 -> vasodilation; no PNS receptors
Skeletal muscle: B2 -> vasodilation; no PNS receptors
Renal: DA -> vasodilation; no PNS receptors
Mesenteric: DA -> vasodilation; no PNS receptors
27
ANS receptors and physiologic action of the bronchial tree
SNS:
B2 -> bronchodilation
Beta 2 receptors are not innervated, instead they respond to catecholamines in the systemic circulation or in the airway (inhaled)
PNS:
M3 -> bronchoconstriction
28
ANS receptors and physiologic action of the kidney
SNS:
Renal tubules: a2 -> diuresis (ADH inhibition)
Renin release: B1 -> increased renin release
PNS:
No receptors
29
ANS receptors and physiologic action of the eye
SNS:
Sphincter muscle (iris): no SNS receptor
Radial muscle (iris): a1 -> contraction (mydriasis)
Ciliary muscle: B2 -> relaxation (far vision)
PNS:
Sphincter muscle: M -> contraction (miosis)
Radial muscle: no PNS receptor
Ciliary muscle: M -> contraction (near vision)
30
ANS receptors and physiologic action of the GI
```
SNS:
Sphincters: a1 -> contraction
Motility & tone: a1 / a2 / B1 / B2 -> Decrease
Salivary glands: a2 -> decrease
Gallbladder & ducts: B2 -> relaxation
```
```
PNS:
Sphincters: M -> relaxation
Motility & tone: M -> increase
Salivary glands: M -> increase
Gallbladder & ducts: M -> contraction
```
31
ANS receptors and physiologic action of the pancreas
SNS:
Islet B cells: a2 -> decrease insulin release and B2 -> increase insulin release
PNS: no receptors
32
ANS receptors and physiologic action of the liver
SNS:
a1 / B2 -> increase serum glucose
PNS: no receptors
33
ANS receptors and physiologic action of the uterus
SNS:
a1 -> contraction
B2 -> relaxation
PNS: no receptors
34
ANS receptors and physiologic action of the bladder
SNS:
Trigone & sphincter: a1 -> contraction
Detrusor: B2 -> relaxation
PNS:
Trigone & sphincter: M -> relaxation
Detrusor: M -> contraction
35
ANS receptors and physiologic action of the sweat glands
SNS: a1 -> increase secretion
PNS: M -> increase secretion
36
Describe alpha 1 stimulation in the eye
Alpha 1 stimulation -> radial muscle contraction -> mydriasis (pupil dilation)
Radial muscle dilates pupil = ready to go = SNS
37
Describe muscarinic stimulation in the eye
Muscarinic stimulation -> sphincter muscle contraction -> miosis (pupil contraction
38
Location of the alpha 2 receptor is throughout the body, but what 3 ways can these locations be classified?
Presynaptic
Postsynaptic
Nonsynaptic
39
What are presynaptic alpha 2 receptors?
These are NE releasing neurons in the CNS and PNS (negative feedback mechanism reduces NE release)
40
Where are postsynaptic alpha 2 receptors located?
In smooth muscle and several organs
41
Where are nonsynaptic alpha 2 receptors found?
Platelets
42
Where are alpha 2 receptors in the nervous system found and what is their physiologic effect? (5)
```
Medulla: decrease SNS tone
Vagus nerve: increase PNS tone
Locus coeruleus: sedation, hypnosis
Spinal cord (dorsal horn): analgesia
???: antishivering
```
43
What the is physiologic effect of alpha 2 receptors in the vasculature?
Vasoconstriction
44
What is the physiologic effect of alpha 2 receptors in the renal tubules?
Inhibits ADH (diuresis)
45
What is the physiologic effect of alpha 2 receptors in the pancreas?
Decrease insulin release
46
What is the physiologic effect of alpha 2 receptors in the platelets?
Increase platelet aggregation
47
What is the physiologic effect of alpha 2 receptors in the salivary glands?
Dry mouth
48
What is the physiologic effect of alpha 2 receptors in the GI tract?
Decrease gut motility
49
Dexmedetomidine is a centrally acting alpha-2 agonist that reduces SNS tone and causes sedation, MAC reduction, analgesia, bradycardia, and vasodilation; what happens with rapid administration?
It can stimulate postsynaptic alpha-2 receptors in the arterial and venous circulations leading to vasoconstriction and hypertension.
- the CNS effect temporarily lags behind
- once it kicks in the central alpha-2 effect overpowers the peripheral alpha-2 effect
- therefore, it is possible to see a transient rise in BP
50
What enzyme metabolizes cyclic adenosine monophosphate? Into what?
Phosphodiesterase III
| AMP - adenosine monophosphate
51
Inhibiting PDE III and increase cAMP benefits:
1. In the cardiac muscle cell, cAMP augments myocardial performance by:
- increasing intracellular calcium and the force of contraction
- increasing the rate of relaxation by accelerating the return of calcium to the sarcoplasmic reticulum (lusitropy)
2. In the vascular smooth muscle cell, cAMP inhibits myosin light chain kinase causing:
- vasodilation
- decreased SVR
52
PDE III inhibitors are also called ______.
| Example
Inodilators
| Milrinone
53
PDE III inhibitors augment myocardial performance independently of the SNS, making them useful in what 4 situation?
BB induced myocardial depression
Acute heart failure
Unresponsiveness to IV catecholamines
Anytime the combination of increased inotropy and reduced afterload would be desirable
54
What is the prototype nonselective phosphodiesterase inhibitor?
Theophylline
55
What is the primary neurotransmitter in the SNS?
Norepinephrine
56
Sympathetic neurons synthesize NE from what 2 substances?
Tyrosine - an amino acid obtained from diet
| Phenylalanine (converted to tyrosine first)
57
Tyrosine is transported into the adrenergic nerve terminal and converted to DOPA by what enzyme? What is significant about this step?
Tyrosine hydroxylase
| This occurs in the cytoplasm and is the rate limiting step in NE synthesis
58
DOPA is converted to dopamine by what enzyme?
DOPA decarboxylase
| This also occurs in the cytoplasm
59
Dopamine is transported into a synaptic vesicles and is converted to NE by what enzyme?
Dopamine beta-hydroxylase
60
In the adrenal medulla, most of the NE is converted to epinephrine by what enzyme?
Phenylethanolamine-N-methyltransferase
61
The adrenal medulla secretes about ___% epinephrine and ____% NE into the circulation
80% EPI
| 20% NE
62
Describe NE release
1. The action potential depolarizes the nerve terminal
2. Voltage-tasted calcium channels open, and calcium flows into the nerve terminal
3. Increased neuronal calcium causes NE vesicles to fuse with the nerve terminal and release NE into the synaptic cleft via exocytosis
4. NE inhibits its release by stimulating the pre-synaptic alpha-2 receptor
5. NE can augment its release by stimulating the pre-synaptic beta-2 receptor
63
What are the 3 ways that NE can be removed from the synaptic cleft? Which is the most important?
Reuptake into the presynaptic neuron (accounts for 80%)
Diffusion away from the synaptic cleft
Reuptake by extraneural tissue
64
Reuptake of NE is blocked by what 2 drugs?
Tricyclic antidepressants
| Cocaine
65
What 2 enzymes metabolize NE and EPI? What is the final metabolic byproduct?
```
Monoamine oxidase (MAO)
Catechol-O-methyltransferase (COMT)
```
Final byproduct of NE and EPI metabolism is vanillylmandelic acid (VMA)
66
An elevated vanillylmandelic acid (VMA) level in the urine aids in the diagnosis of what?
Pheochromocytoma
67
Where are the principle sites of metabolism of catecholamines that have entered circulation?
Liver and kidneys
Only ~5% of NE is excreted unchanged in the urine
68
Vanillylmandelic acid (VMA) has another name
3-methoxy-4-hydroxymandelic acid
69
What is the primary neurotransmitter in the parasympathetic nervous system?
Acetylcholine
70
Acetylcholine stimulates how many different receptor types? What are they and where are they found?
3:
Nicotinic type N (nerve): preganglionic fibers at autonomic ganglia (SNS & PNS), central nervous system
Nicotinic type M (muscle): neuromuscular junction
Muscarinic: postganglionic PNS fibers at effector organs, central nervous system
71
Nicotinic receptors are what type of receptor? Muscarinic receptors are what type?
Nicotinic: ion channels
Muscarinic: GPCR
72
Describe Ach synthesis
1. Choline is transported from the blood into the cytoplasm of the nerve terminal
2. Acetyl Coenzyme A is produced in the mitochondria and released into the cytoplasm
3. In the presence of the enzyme choline acetyltranferase, choline and acetyl CoA are joined to form acetylcholine
4. Acetylcholine is packed into vesicles
73
Describe the release of Ach
1. The action potential depolarizes the nerve terminal
2. Voltage-gated Ca+2 channels open and allow an influx of Ca+2 into the nerve terminal
3. Ca+2 is required for Ach vesicles to fuse with the nerve terminal and release Ach via exocytosis into the synaptic cleft
74
Why does Mg+2 cause muscle weakness and act synergistically with NMB?
Mg+2 is an antagonist of Ca+2 at the presynaptic nerve terminal
75
Describe Ach metabolism
1. Acetylcholinesterase is positioned around the cholinergic receptor and quickly hydrolyzes Ach after it unbinds from the receptor
2. The byproducts are choline and acetate
3. Choline is transported back into the nerve terminal via reuptake and will serve as substrate for further Ach synthesis
4. Acetate diffuses away from the synaptic cleft
76
Preganglionic nerve fibers in the SNS are what type of nerve fibers?
Myelinated B fibers
77
Postganglionic nerve fibers in the SNS are what type of fibers?
Unmyelinated C fibers
78
List the 5 components of the autonomic reflex arc
```
Sensor
Afferent pathway
Control center
Efferent pathway
Effector
```
79
What structures receive the bulk of sensory input from the body? (3)
Hypothalamus
Brainstem
Spinal cord
80
Compare and contrast the architecture of the SNS and PNS efferent pathways
SNS:
Preganglionic: short, myelinated, B-fibers, releases Ach
Postganglionic: long, unmyelinated, C-fibers, releases NE (except sweat glands, piloerector muscles and some vessels release Ach)
PNS:
Preganglionic: long, myelinated, B-fibers, release Ach
Postganglionic: short, unmyelinated C-fibers, release Ach
81
The SNS originates where? What spinal nerves? Where are the cell bodies? Where do the axons exit?
Thoracolumbar
T1 - L3
Cell bodies arise from the intermedia lateral region of the spinal cord
Axons exit via the ventral root
82
Where is the ganglia of the SNS?
Near the spinal cord
83
Post to preganglionic ratio of the SNS
30: 1 -> post-synaptic amplification contributes mass response
84
SNS preganglionic fibers
Short
Myelinated
B-fibers
85
Post ganglionic SNS fibers
Long
Unmyelinated
C-fibers
86
Neurotransmitter and ganglia in SNS
Ach
87
Receptor at the ganglia is SNS
Nicotinic type N
88
Neurotransmitter from postganglionic fiber in SNS
NE (except sweat glands, piloerectory muscles, so vessels release Ach)
89
Receptor at effect organ in SNS
Alpha
Beta
Dopamine
Muscarinic (for the Ach exceptions)
90
The PNS originates where? What spinal nerves? What cranial nerves?
Craniosacral
CN III, VII, IX, X
S2 - S4
91
Where is the ganglia in the PNS?
Near or inside the effector organ
92
What is the post to preganglionic ration in the PNS?
1-3 : 1 -> precise control of each organ
93
Preganglionic fiber in the PNS
Long
Myelinated
B-fiber
94
Postganglionic fiber in the PNS
Short
Unmyelinated
C-fiber
95
Neurotransmitter at the ganglia in the PNS
Ach
96
Receptor at the ganglia in the PNS
Nicotinic type N
97
Neurotransmitter from postganglionic fiber in the PNS
Ach
98
Receptor at effector organ in PNS
Muscarinic
99
In the SNS the preganglionic sympathetic fibers exit the spinal cord via the what? Through what do the fibers enter the sympathetic chain?
Ventral nerve roots
| White communicating rami
100
Once inside the sympathetic chain, what are the 3 paths a preganglioic fiber can take to synapse with a postganglionic fiber?
1. It will synapse with the postganglionic fiber and exit at the same level
2. It will ascend or descend the sympathetic chain, then synapse at another level before exiting
3. It will bypass the sympathetic chain entirely and synapse in a collateral ganglion
101
After synapsing in the ganglia, the postganglionic fiber will travel where?
To its respective effector organ
102
Fibers that innervate the sweat glands, piloerector muscle, and blood vessels to the skin and muscles take a different path than the rest of the SNS postganglionic fibers, what path do they take?
After exiting the sympathetic chain, the re-enter the spinal nerve via the grey communicating rami, and then they travel alongside somatic nerves towards their effector organ
103
What provides sympathetic innervation to the ipsilateral upper extremity and a portion of the head and neck?
Stellate ganglion
104
Stellate ganglion blockade
Treatment of upper extremity sympathetic dystrophy
Complex regional pain syndrome
Increase blood flow to the upper extremity
Often an unintended consequence of a brachial plexus block
105
What manifests from blockade of the Stellate ganglion?
Horner’s syndrome:
Ptosis, anhidrosis, miosis, and enophthalmos
Mnemonic: Very Homely PAM- vasodilation Horner ptosis anhidriosis miosis
106
Name 2 areas of the adrenal gland and what they secrete
Medulla: catecholamines
Cortex: glucocorticoids, mineralocorticoids, androgens
107
How is the innervation of the adrenal medulla different from the typical SNS efferent architecture?
There is no postganglionic fiber.
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% to 20% respectively
108
Chromaffin cells are derived from what type of tissue?
Neural tissue
109
At rest, the adrenal medulla secretes how much EPI? NE?
EPI: 0.2 mcg/kg/min
NE: 0.05 mcg/kg/min
110
How long do catecholamines remain in the blood stream compared who the synaptic cleft?
Remain the bloodstream 5 - 10 times longer than in the synaptic cleft
111
What is a pheochromocytoma?
A catecholamine secreting tumor (mostly NE) that usually originates in the chromaffin tissue in the adrenal gland
112
Classic presentation of pheochromocytoma
Excessive SNS activation: headache, diaphoresis, tachycardia
113
What is the hemodynamic management of a patient with pheochromocytoma? What must you do FIRST?
You must block alpha before you block beta!
Alpha antagonists commonly used:
-nonselective - phenoxybenzamine, phentolamine
-alpha-1 selective - doxazosin, prazosin
114
What problems arise from blocking the beta receptor first with pheochromocytoma?
Beta-2 blockade inhibits skeletal muscle vasodilation and increases SVR
Beat-1 blockade reduces inotropy and can precipitate CHF in the setting of increased SVR
115
Once the tumor is removed what happens to catecholamine levels?
They all go with it, prepare for hypotension and hypoglycemia
116
Sympathetic stimulation causes hepatocytes to release what 2 things into systemic circulation?
Glucose and potassium
117
What happens to the GLU released by the liver with SNS stimulation?
It provides substrate for aerobic metabolism, but for cells to utilize GLU insulin must be present, so it would make sense that SNS stimulation causes the pancreas to release insulin from the beta cells
118
What happens to the potassium released by the liver with SNS stimulation?
Initially K+ released from the liver causes the serum K+ to rise - short lived.
SNS stimulation causes adrenal medulla to secrete catecholamines into circulation.
When EPI binds to the B2 receptor on skeletal muscle and RBCs, it activates the Na/K pump and shifts K+ into the cells -> decrease in serum K+
119
Name 4 ways to shift K+ into the cell
Alkalosis
Beta-2 agonists (albuterol, ritodrine, epi)
Theophylline (methylxanthines)
Insulin (activating the Na/K exchanger: epi or insulin)
120
Name 4 ways to shift K+ out of the cell
```
Acidosis (activating H+/K+ exchanger)
Cell lysis (rhabdomyolysis)
Hyperosmolarity
Succinylcholine (nicotinic type-m agonism)
```
121
What is the baroreceptor reflex?
It regulates short term BP control
- when BP rises the BRR decreases HR, contractility and SVR
- when BP falls the BRR increases HR, contractility and SVR
122
If the baroreceptor reflex regulates short term BP, what regulates longer term BP?
RAAS and ADH
123
Where are the stretch receptors for the baroreceptor reflex?
Carotid sinus
| Transverse aortic arch
124
On what nerve is afferent information from the stretch receptors in the carotid sinus sent?
Nerve of Hering -> glossopharyngeal nerve -> nucleus tractus solitarius in the medulla
125
On what nerve does the stretch receptors in the transverse aortic arch send afferent information?
Vagus nerve -> nucleus tractus salitarius in the medulla
126
What is the main control center for the baroreceptor reflex?
The vasomotor center in the medulla and in the pons
127
What are the 4 key functions of the vasomotor center?
Vasoconstriction
Vasodilation
Cardiac stimulation
Cardiac inhibition
128
List 3 clinical examples of the baroreceptor reflex and their result
Carotid endarterectomy - manipulation of carotid sinus may cause bradycardia.
Mediastinoscopy - pressure from the scope on the transverse aortic arch may cause bradycardia.
Phenylephrine - agonism of the alpha-1 receptor increase SVR and BP, the baroreceptor reflex increase vagal tone causing the HR to decrease.
129
How do VAs affect the baroreceptor reflex? Which one affects it this way the least and why?
Decrease effectiveness of baroreceptor reflex in a dose-depends fashion.
ISO has mild beta-1 agonist properties, it impairs the baroreceptor reflex the least.
130
How does thiopental affect the baroreceptor reflex
Preserves baroreceptor function - causes SVR to decrease with a compensatory rise in HR
131
How does propofol affect the baroreceptor reflex?
Depresses baroreceptor function
132
How does ketamine affect the baroreceptor reflex?
It activates the SNS and will cause an increased HR with a minimal change is SVR. If catecholamine reserve is exhausted, direct myocardial depressant effects may be unmasked.
133
How does Etomidate affect baroreceptor reflex?
Usually an unchanged HR with a small decrease in SVR, hypovolemia patients may experience hypotension following Etomidate
134
How does hydralazine affect the baroreceptor reflex?
Intact. It is a potent vasodilator, the reduction in SVR is countered with an increase in HR via the BRR.
135
How does nitroprusside and Nitroglycerine affect the baroreceptor reflex?
Preserved BRR
136
How do beta adrenergic blockers affect the baroreceptor reflex?
By antagonizing the beta-1 receptor in the heart, BB may, depending on the extent of beta blockade, prevent a compensatory rise in HR in the setting of hypotension. Labetalol also antagonizes the alpha-1 receptor and may increase the risk of Orthostatic hypotension
137
How does norepinephrine affect the baroreceptor reflex?
Its effect on HR is dose-dependent. In lower doses the beta-1 chronotrophic effects prevail. As the dose increase, the alpha-1 vasoconstrictive effects overshadow the beta-1 effects. The net results is a baroreceptor-mediated fall in HR.
138
How do epi, dobutamine, isoproterenol and dopamine affect the baroreceptor reflex?
They all increase HR regardless of their dose.
139
Drugs that decrease BP and increase HR, BRR is _____
Preserved
Hydralazine
Thiopental
140
Drugs that increase BP and decrease HR, BRR is ______
Preserved
| Norepinephrine
141
Drugs that decrease BP and HR, BRR is _____
Inhibited
Labetalol
Sevoflurane
142
Drugs with variable response, HR can increase, decrease, stay the same, or stop entirely):
Propofol
143
What is the Bezold-Jarisch Reflex?
Slows HR in the setting of profound hypovolemia (preload is too low)
144
What is the Bainbridge reflex?
Increases HR in the setting of venous congestion (preload is too high)
145
What is the stimulus for Bezold-Jarisch reflex?
Venous return too low
| Myocardial ischemia
146
What is the purpose of the Bezold-Jarisch reflex?
Allows empty heart time to fill
| A slow heart is a better perfused heart
147
Where are the sensors for the Bezold-Jarisch reflex?
Left ventricle (but also in other cardiac chambers)
148
What is the afferent nerve for the Bezold-Jarisch reflex?
Vagus: unmyelinated C fibers
149
What is the control center for the Bezold-Jarisch reflex?
Medulla: vasomotor center
150
What the the efferent nerve for the Bezold-Jarisch reflex?
Vagus stimulation
151
What is the effector site(s) for the Bezold-Jarisch reflex?
SA node: decrease HR
| AV node: decrease CV
152
What is the clinical response of the Bezold-Jarisch reflex?
Triad: bradycardia, hypotension, coronary artery dilation
153
What is the treatment for Bezold-Jarisch reflex?
Restore preload: IVF, T-burg, elevate legs above head
| Increase HR: atropine, ephedrine, epinephrine
154
List 4 examples that will stimulate Bezold-Jarisch reflex?
Profound hypotension
Massive hemorrhage
Cardiac arrest under spinal anesthesia
Shoulder arthroscopy and interscalene block and epi in LA and sitting position
155
What it the stimulus for the Bainbridge reflex?
Venous return too high
156
What is the purpose of the Bainbridge reflex?
Minimizes venous congestion and promotes forward flow
157
Where are the sensors for the Bainbridge reflex?
SA node (SA node stretch directly increases its firing rate)
Right ventricle
Pulmonary veins
158
What is the afferent nerve for the Bainbridge reflex?
Vagus: unmyelinated C fibers
159
What is the control center for the Bainbridge reflex?
Medulla: vasomotor center
160
What is the efferent nerve for the Bainbridge reflex?
Vagus inhibition
161
What is the effect site for the Bainbridge reflex?
SA node: increase HR
162
What is the clinical response of the Bainbridge reflex?
Tachycardia
163
What is the treatment for Bainbridge reflex?
None needed
164
What are examples that will trigger the Bainbridge reflex?
Autotransfusion during childbirth
| Very rapid administration of IVF
165
Other than triggering the Bainbridge reflex, what other 2 things does cardiac congestion lead to?
1. Decreased ADH release from the posterior pituitary gland
| 2. Increased atrial natriuretic peptide release -> diuresis -> decreases intravascular volume
166
What is another name for the oculocardiac reflex? Why?
Five & dime reflex:
Afferent limb: CN V - trigeminal nerve
Efferent limb: CN X - vagus nerve
167
What stimuli can trigger the oculocardiac reflex?
Traction to the extraocular muscles (especially the medial rectus)
Strabismus surgery - particularly in children
Pressure on the globe
Pressure on the conjunctiva
Ocular trauma
Pressure on the orbital tissue that remains following enucleation
A retrobulbar block can either cause or prevent the oculocardiac reflex
168
What is the afferent limb of the oculocardiac reflex?
Long & short ciliary nerve -> ciliary ganglion -> ophthalmic division V1 of trigeminal nerve (CN V) -> gasserian ganglion
169
What is the control center for the oculocardiac reflex?
Medulla: vasomotor center
170
What is the efferent limb of the oculocardiac reflex?
Vagus (CN X)
171
What is the effector organ of the oculocardiac reflex?
Heart: M2 receptor at SA and AV nodes
172
What is the clinical presentation of the oculocardiac reflex?
```
Bradycardia
Hypotension
Junctional rhythm
AV block
Asystole
```
173
List 3 factors that worsen severity of the oculocardiac reflex?
Hypoxemia
Hypercarbia
Light anesthesia
174
What is the treatment for oculocardiac reflex?
Ask surgeon to remove stimulus
Administer 100% O2, ensure proper ventilation, and deepen anesthetic
Administer an anticholinergic such as atropine or glycopyrrolate
175
The oculocardiac reflex will fatigue with subsequent occurrences. T/F
T
176
Will anticholinergic pretreatment help prevent oculocardiac reflex?
Barash says no
| Nagelhout says yes for peds
177
What is the Cushings reflex?
A sign of intracranial hypertension
Presentation: Hypertension, bradycardia, and irregular respirations
HTN is attempt to restore CPP
Bradycardia is from the baroreceptor reflex’s response to HTN
Irregular respirations are the result of brainstem compression
178
What is the celiac reflex?
It is initiated by traction to the mesentery or other abdominal organs.
It is mediated by the vagus nerve.
It causes bradycardia and hypotension.
179
What is the chemoreceptor reflex?
It is stimulated by hypoxia and hypercarbia.
| It increases minute ventilation and SNS tone.
180
What is the primary determinant of cardiac output in the patient with a heart transplant? What is the consequence of this?
The transplanted heart is severed from autonomic influence, so the HR is determined by the intrinsic rate of the SA node. This explains with these patients often have a resting tachycardia (HR = 100-120 bpm).
If CO is the product of HR and SV and the HR is fixed, then CO becomes dependent on preload. Indeed, CO is highly dependent on cardiac filling. This feature makes these patients very sensitive to hypovolemia.
181
What drugs can be used to augment HR in the patient with a heart transplant?
Central to understanding this is knowing there is no autonomic input from the cardiac accelerator fibers (T1-T4) or the vagus nerve.
Drugs that directly stimulate the SA node can be sued to increase HR: epi, isoproterenol, glucagon.
Drugs that indirectly simulate the SA node can NOT be used: atropine, glycopyrrolate, ephedrine
182
Any reflex that requires ANS innervation will be disrupted in the denervated heart, except for which reflex? Why?
Bainbridge reflex, because SA node stretch will directly increase SA node firing rate
183
What is the most common cause of cardiac denervation in non-cardiac surgery patients?
Diabetes (diabetic autonomic dysfunction)
184
What is a glomangioma?
Glomus tumor: originates from neural crest cells, usually not malignant.
Tend to grow in the neuroendocrine tissues that lay near carotid artery, aorta, glossopharyngeal nerve, and the middle ear.
185
What substance(s) do glomaniomas secrete and what are their effects? What are your primary concerns for anesthetic?
They secrete several vasoactive substances that can lead to exaggerated hyper- or hypotension.
- Norepinephrine (similar to pheochromocytoma): HTN
- Serotonin and kallikrein (similar to carcinoid tumor): bronchoconstriction< HA, HTN, flushing, and diarrhea
- Histamine or bradykinin: bronchoconstriction and hypotension
- these tumors do not release epi because they lack the enzyme that converts NE to epi (phenylethanolamine N-methyltransferase)
- Octreotide can be used to treat carcinoid-like s/sx
- Cranial nerve dysfunction can cause swallowing impairment, aspiration of gastric contents, and airway obstruction
- Surgical dissection fo a glomus tumor that has invaded the internal jugular vein increases the risk of air embolism
186
What are the anesthetic consideration for multiple system atrophy? Aka?
Shy-Drager syndrome: causes degeneration of locus coeruleus, intermedia lateral column of the spinal cord (where the cell bodies for the SNS efferent nerves live), and the peripheral autonomic nerves.
S/sx reflect autonomic dysfunction: orthostatic hypotension, urinary retention, impotence, and bowel dysfunction.
Death from cerebral hypoperfusion usually occurs within 8 years of initial diagnosis.
Autonomic dysfunction contributes to hemodynamic instability during anesthesia. Hypotension is treated with volume resuscitation and direct acting sympathomimetics. Indirect acting adrenergic agonists (ephedrine) and possibly ketamine can cause an exaggerated hypertensive response.
187
What receptors does norepinephrine affect?
Dose dependent affinity for:
Alpha-1
Alpha-2
Beta-1
188
Low dose vs high dose norepinephrine?
Dose: 0.02 - 0.04 mcg/kg/min
Low dose range: beta-1 selective (increases HR and inotropy)
High dose range: stimulates alpha-1, alpha-2, and beta-1 receptors (increase SVR -> increase BP -> decreases HR via baroreceptor reflex)
189
Norepinephrine is ideal for low ____ states, like sepsis or CPB hypotension due to low _______.
SVR
| Afterload
190
Why should norepinephrine be avoided in cardiogenic shock?
Because it increases afterload and MVO2 (myocardial oxygen consumption)
191
What should be done if norepinephrine extravasation occurs?
Inject area with phentolamine 2.5-10 mg in 10mL of diluent to vasodilate the affected region.
A stellate ganglion block is another option.
192
Compare and contrast low, intermediate, and high dose epinephrine.
Low dose 0.01-0.03 mcg/kg/min: beta-1, beta-2 (increased HR, CO and inotropy, decreased SVR and wide pulse pressure)
Intermediate dose 0.03-0.15 mcg/kg/min: mixed alpha and beta effects
High dose > 0.15 mcg/kg/min: alpha effects predominate, and supraventricular tachyarrhythmias are common
193
What effects does epi have on bronchials?
Bronchodilation
194
What effect does epi have on mast cells?
Mast cell stabilization - useful for anaphylaxis
195
What effect does epi have on LAs?
Prolongs duration of LAs
196
What effect does epi have on serum glucose?
Increases serum glucose
197
What effect does epi have on serum K+?
Causes hypokalemia due to transcellular potassium shift
198
Compare and contrast low, intermediate, and high dose dopamine
Low dose 1-2 mcg/kg/min: renal vasodilation and increased RBF (BP may decrease as more CO is delivered to the kidneys).
Intermediate dose 2-10 mcg/kg/min: cardiac stimulation (increased HR, inotropy and CO)
High dose 10-20 mcg/kg/min: vasopressor effect (alpha effects overshadow DA and beta effects)
199
Does renal dose dopamine reduce morbidity or mortality and prevent renal failure?
No, no, and no.
200
What receptors does isoproterenol stimulate? Dose?
Beta-1 and beta-2 receptors
| 0.02-0.05 mcg/kg/min
201
Describe the cardiovascular effects of isoproterenol
Cardiac stimulation - increased HR, inotropy and CO
Vasodilation decreases SVR
The reduction in SVR can be so severe as to drop DBP, and this can impair CPP (CPP = AoDBP - LVEDP)
This makes it a poor choice for septic shock
It can cause severe dysrhythmias and tachycardia
202
List 4 clinical indications for isoproterenol
Chemical pacemaker for bradycardia unresponsive to atropine
Heart transplant
Treatment of bronchoconstriction
Cor pulmonale
203
What receptors does dobutamine stimulate? Dose? Effects?
Potent beta-1 and mild beta-2 agonist
0.5-15 mcg/kg/min
Cardiac stimulation - increased HR, inotropy, and CO
204
What receptors does phenylephrine stimulate?
Dose
Infusion
Non-catecholamine that selects for alpha-1 receptors (no beta effects)
Bolus dose 20-100 mcg
Infusion 10-200 mcg/min
205
What cardiovascular effects does phenylephrine have?
Increases SVR
Increases coronary perfusion pressure
Reflex bradycardia
Useful for conditions where increased afterload is required, such as hypertrophic cardiomyopathy or tetralogy of Fallot
206
What receptors does ephedrine stimulate?
| Dose
Non-catecholamine with direct and indirect effects at alpha-1, alpha-2, beta-1 and, beta-2
IV dose 5-10 mg
IM dose 25-50 mg
207
What cardiovascular effects does ephedrine have?
Increases HR, inotropy, CO, and SVR
Uses endogenous catecholamine stores from the presynaptic sympathetic nerve
Multiple doses can cause tachyphylaxis (progressively smaller response to a given dose after multiple administrations)
208
In what situations should ephedrine NOT be used to treat hypotension?
Does not work well when neuronal catecholamine stores are depleted (sepsis) or absent (heart transplant)
Risk of hypertensive crisis in patient on MAO inhibitors
Conditions where increased HR or contractility is detrimental to hemodynamics
209
Where is vasopressin produced? What releases vasopressin?
Produced by hypothalamus
| Released by the posterior pituitary gland
210
How does vasopressin increase BP?
Vasopressin restores BP in 2 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.
211
What is the important difference between aldosterone and vasopressin?
Aldosterone increases water and sodium reabsorption (serum osmolarity is unchanged); vasopressin only increases water reabsorption so serum osmolarity is lowered
212
Vasopressin bolus? Infusion? Overdose?
IV bolus 0.5-1 unit
IV infusion 0.01-0.04 units/min
Overdose can cause hyponatremia and seizures
213
What is the first line treatment for ACEI or ARB induced vasoplegia that’s refractory to catecholamines? Second line therapy?
First: Vasopressin
Second: Methylene blue
214
Mnemonic for Beta-1 selective beta antagonists
MABE AB
Metoprolol
Atenolol
Betaxolol
Esmolol
Acebutolol
Bisoprolol
215
Non selective beta antagonists (6)
```
Carvedilol
Labetalol
Nadolol
Pindolol
Propranolol
Timolol
```
216
Clinical uses of BBs (8)
```
Essential HTN
Angina pectoris
Coronary artery dz
Myocardial ischemia
Dysrhythmias
Congestive heart failure
Hyperthyroidism
Migraine headaches
```
217
What is the primary site of metabolism of the commonly used BBs? What are 2 exceptions?
Most BBs depend on the liver as their primary site of metabolism.
Exceptions:
Esmolol - RBC esterases
Atenolol - eliminated by the kidneys
218
What are the cardiovascular effects of BBs?
Reduce HR, inotropy, conduction velocity, and myocardial oxygen demand
219
What is the significance of NON-selective BBs?
Increase airway resistance, in patients with asthma a cardio selective BB is the best option.
220
What BBs antagonize the alpha-1 receptor?
Labetalol block beta to alpha 7:1
| Carvedilol block beta to alpha 10:1
221
How can BB overdose be treated?
```
Glucagon
Calcium
PDE III inhibitors
Epinephrine
Isoproterenol
Cardiac pacing
```
222
Prop BB may reduce the risk of what? But increase the risk of what?
Reduce risk: cardiac morbidity and mortality
| Increase: stroke, bradycardia, and hypotension
223
Which BBs have LA 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 cardia action potential, however it probably only occurs when these drugs reach toxic levels.
Propranolol
Acebutolol
224
What is intrinsic sympathomimetic activity? Which drugs exert this effect?
BB 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.
Labetalol
Pindolol
225
List 4 alpha antagonists
Phenoxybenzamine
Phentolamine
Prazosin
Yohimbine
226
Describe Phenoxybenzamine
Long acting, non-selective, noncompetitive antagonist of the alpha-1 and alpha-2 receptor.
Causes vasodilation by decreasing SVR.
Impairs the NE regulating effect of the presynaptic alpha-2 receptor -> reflex tachycardia.
Its primary role is to manage HTN in the patient with pheochromocytoma 0.5-1 mg/kg PO.
Side effects: orthostatic hypotension and nasal congestion.
227
Describe phentolamine
Short-acting, non-selective, competitive antagonist of the alpha-1 and alpha-2 receptor.
It causes vasodilation by decreasing SVR.
It impairs the NE regulating effect of the presynaptic alpha-2 receptor -> reflex tachycardia.
Clinical uses include tx of pheochromocytoma or autonomic hyperreflexia 30-70 mcg/kg IV.
Can also be injected into tissue surrounding an infiltrated IV containing a vasoconstrictor 2.5-10 mg in 10mL diluent.
228
Describe prazosin
Selective alpha-1 blocker.
Causes vasodilation by decreasing SVR.
Does not impact NE regulating effect of the presynaptic alpha-2 receptor so no reflex tachycardia.
Clinical uses: essential HTN, especially in patients with benign prostatic hypertrophy.
229
Describe yohimbine
An herb that antagonizes the alpha-2 receptor.
Increases sympathetic tone by increasing NE release from the presynaptic nerve terminal.
Used to treat orthostatic hypotension.
Overdose leads to tachycardia and HTN.
