Basic neurophysiology

Question 1

Glutamate agonizes which 3 receptors? Is glutamate excitatory or inhibitory? How are action potentials generated?

Answer 1

In the CNS, glutamate is a major excitatory neurotransmitter and there are three main receptor targets: AMPA, Kainate, and NMDA receptors.
Glutamate receptor agonism results in the flow of cations across a channel. With this flow of sodium (and in some cases calcium) into the cell, and potassium out of the cell, the resting membrane potential of the cell changes and thus generates an action potential.

Question 2

Is GABA excitatory, or inhibitory? How does it work-GABA A vs GABA B?

Answer 2

GABA is a major inhibitory neurotransmitter in the CNS, which in the case of the GABA-A receptor, opens chloride channels, hyperpolarizing them and making the generation of action potentials more difficult.
The GABA-B receptor also responds to GABA but works through a second messenger and does not involve chloride channels.

Question 3

NMDA-excitatory or inhibitory? What does it let in? What does it let out? What excites it? What blocks it?

Answer 3

NMDA receptors are excitatory and allow Na+ and Ca++ in and K+ out. Glutamate excites this receptor and leads to membrane depolarization. There are multiple substances that can antagonize this receptor, therefore making depolarization (and in the spinal cord pain transduction) less likely (inhibited). The two substances you need to know are ketamine (which binds at the PCP binding site) and Mg++. Remember this is not a complete description, please crack open your favorite text and read more.

Question 4

The agonism of the opioid receptor results in:

A. Changing the resting potential to be less negative
B. Changing the resting potential to be more negative
C. Changing the threshold potential to be less negative
D. Changing the threshold potential to be more negative

Answer 4

B: Changing the resting potential to be more negative

To answer this tricky question you need to first know that the opioid receptor activation results in neuronal hyperpolarization (making it more difficult to generate an action potential)

Opioid agonism probably changes only the resting potential and not the threshold potential (in other words, generation of an action potential still requires a certain positive inflection of mV, its just starting from a more negative point)

Question 5

In the setting of starvation, which of the following substances will the brain increase the utilization of most to provide a source of energy:

Answer 5

Ketones

Normally glucose provides the overwhelming majority of ATP for energy utilized by the brain, but in starvation (after 3 days) glucose utilization by the brain decreases by about 25% and ketone utilization increases by 1300%!

Question 6

Among all the cellular processes of the brain (maintenance, transportation, metabolism, synaptic transmission),________ is the largest consumer of energy

Answer 6

electrical activity (transporting ions across the cell membranes to maintain a resting potential and fire action potentials)

Question 7

What is coupling? Which drugs de-couple? How much CO does the brain need to receive?

Answer 7

when less energy is being used by the brain, less oxygen is delivered.
the degree of cerebral blood flow is coupled to the cerebral metabolic rate)
Other drugs decouple this relationship, such as fluorinated volatile anesthetics. In this case, despite less energy being consumed, more oxygen is delivered (increased blood flow). Under normal circumstances, the brain needs to receive about 15-20% of cardiac output to cover the metabolic needs

Question 8

Look at #5 graph in this basic neurophys section

Answer 8

Ok

Question 9

Is BIS reliable for global ischemia due to hypotension?

Answer 9

Also because general anesthesia shares many features with brain ischaemia, processed EEG (BIS monitor, etc) is not a reliable monitor for this issue.

Question 10

Which volatile anesthetic is NOT a cerebral vasodilator?

Answer 10

N2O

Question 11

Highest CBF and intracranial pressure with the volatile (main 3)

Answer 11

Of the anesthetics you’ll be expected to know, CBF is highest with isoflurane, followed by desflurane, followed by sevoflurane (at a given MAC). Because of the increased CBF, intracranial pressure tends to increase with volatile anesthetics (highest with desflurane, then isoflurane, then sevoflurane)

Question 12

Brain is a fixed space-explain what can increase that pressure? What’s normal ICP? And above what number do neurological symptoms start to show?

Answer 12

The cranial vault is a fixed space and any increase in brain mass (usually from swelling or malignancy), CSF production or decreased CSF absorption, or increased blood volume from increased CBF will increase ICP. Normal ICP is less than 10 mm Hg and above 20 cm Hg, the pressure volume relationship is such that small increases in increased volume will lead to exponentially large increases in pressure.

Sustained very high ICP (well above 20 mm Hg, more like 40 mm Hg+) can result in brain herniation and death. This is discussed in more detail in the clinical neurophys section. What is important to tell from the graph is that the change from normal to danger zone (20 mm Hg) to life threatening (40+ mm Hg) can all occur with a very small volume change (because the pressure-volume relationship increases exponentially). Now you know why you’re doing a hemicrani at 2 am on a patient with an MCA stroke prior to malignant swelling.

Question 13

When auto regulation is interrupted such as a pathological state like trauma or stroke, blood volume increases in relation to blood pressure.
T/F

Answer 13

True

Question 14

Propofol, etomidate, and many barbituates including thiopental decrease CBF and increase what?

Answer 14

these agents (especially the first three) cause an increase in cerebral vascular resistance.

Question 15

In general, what do opioids do to CBF? What are the two exceptions?

Answer 15

In general, opioids will slightly decrease CBF. Primarily Sufenta and fentanyl

Question 16

Which substances can NOT cross the BBB?

Answer 16

Electrolytes, mannitol, glucose, dextrose, amino acids, proteins, and hydrophilic compounds cannot cross.

Question 17

Which of the following decrease the production of cerebral spinal fluid:

A. Mannitol
B. Furosemide
C. Fentanyl
D. Ketamine

What other drug does this?

Answer 17

Furosemide

This is trivial, admittedly, but it is a board classic! That is why this is the second time this is discussed in the M5 for such a small piece of minutiae. There are two drugs you should know that decrease CSF production and those are acetazolamide and furosemide (acetazolamide is more commonly used for this purpose).

Question 18

Opioids and barbiturates and how they relate to CSF

Answer 18

Fentanyl and other opioids probably have little to no effect on CSF production, although they do increase CSF absorption, and the same is for benzodiazepines, barbituates, and etomidate (more important minutiae)

Question 19

Lidocaine and CBF and CMR

Answer 19

Most IV anesthetics such as propofol, etomidate, barbituates, and to a lesser extent benzodiazepines, will decrease CMR and CBF. Lidocaine acts just like these IV anesthetics in that both CBF and CMR are decreased.

Question 20

As compared to the serum, which of the following has proportionately the lowest levels in the CSF:

A. Protein
B. Sodium
C. Bicarbonate
D. Glucose

Osmolality of CSF and serum are the same? pH of serum vs CSF?

Answer 20

Normal CSF has about the same concentration of sodium as the serum, moderately lower concentrations of other cations, increased chloride, slightly decreased bicarbonate and glucose, but far lower levels of protein (7,000 mg/dL in serum and 28 mg/dL in CSF). The osmolality of CSF and serum are the same. The pH of normal serum is 7.4 and normal CSF is 7.3.

Question 21

Class a nerves: 
Alpha delta
A-alpha 
A-beta 
A-gamma

Answer 21

Class A nerves are large and myelinated and have further subdivisions.
A-delta nerves are myelinated, have a low threshold for activation, and conduct signal fast-they deal with nociception. A-alpha fibers are used for motor and proprioception. A-beta and A-gamma are used for cutaneous touch, pressure and muscle spindles.

Question 22

Class C nerves are used in:

A. Nociception
B. Preganglionic autonomic system
C. Post-ganglionic autonomic system
D. A & B
E. A & C

Answer 22

E.

Class C fibers are non-myelinated or lightly myelinated nerves with slow conduction velocities. Slow-pain and post-ganglionic conduction are mediated through these nerves

Question 23

Pain signal:

Answer 23

The first order neuron has a cell body in the dorsal root ganglion and sends fibers to the periphery (where nociceptors can be activated), and sends the signal through the dorsal root ganglion (in most cases but not all) and synapses on the second order neuron in the dorsal horn of the spinal cord (as well as a variety of other places including sympathetic nerves in the dorsal root). The second order neuron’s cell body is also in the dorsal horn of the spinal cord and sends the transmission to the contralateral hemisphere of the spinal cord (in many cases but not all) and sends signal up the spinothalamic tract (in some cases but not all) and synapses in a variety of places, with the three most important being: reticular formation, periaqueductal gray, and thalamus.

Question 24

Which of the following increases in response to pain:

A. Cortisol
B. Antidiuretic hormone (ADH)
C. Cellular and humoral immune function
D. A&B
E. All of the above

Answer 24

D: A&B

Cortisol, angiotensin II, ADH, catecholamines, cytokines, adrenocorticotropic hormone, growth hormone, & glucagon increase in response to pain. Cellular and humoral immune function decreases. Pain is associated with a stress response independent of surgery.

Question 25

What things increase in response to pain?

Answer 25

D: A&B

Cortisol, angiotensin II, ADH, catecholamines, cytokines, adrenocorticotropic hormone, growth hormone, & glucagon increase in response to pain. Cellular and humoral immune function decreases. Pain is associated with a stress response independent of surgery

Question 26

In what area of the brain is pain SENSED?

Answer 26

Post-central gyrus

Question 27

Which of the following help explain hyperpathia:

A. Peripheral nociceptor sensitization
B. Spinal cord sensitization
C. Wind-up
D. All of the above

Explain them all

Answer 27

Which of the following help explain hyperpathia:

A. Basically peripheral sensitization means that the nociceptors require less stimulus to fire off an action potential, they send more action potentials once they’re stimulated, the receptors are up-regulated, and even after the stimulus ends, they can still fire off action potentials. Numerous factors are responsible for this sensitization process, including bradykinin, prostaglandin, histamine, among many others.

B. In the spinal cord the same thing happens in that nociceptive second order neurons are sensitized (takes less stimulus to be incited, will fire more action potentials after incited, and will continue to fire after the stimulus is gone).

Question 28

Spinothalamic tract: Lateral: Location, intensity, duration.
Ventral: Autonomic and emotional
Spinoreticular tract: Arousal and autonomic
Spinomesencephalic tract: Activates anti-nociceptive pathways
Spinohypothalamic tract: Hypothalamus and emotions
Spinotelencephalic tract: Hypothalamus and emotions
Spinocervical tract: Alternative pathway
Dorsal columns (gracile fasciculus and fasciculus): Alternative pathway

NOTED.

Answer 28

But you do need to know there are multiple ascending pathways in the spinal cord that carry nociceptive signals.

Question 29

Cholinergic fibers for para and sympathetic both ore and post

Answer 29

Both the sympathetic and parasympathetic system have cholinergic preganglionic fibers. All postganglionic parasympathetic fibers are also cholinergic. Most postganglionic sympathetic fibers are adrenergic, except sweat glands and some blood vessels. The boards often will focus on the exceptions to the rule, so don’t forget these two exceptions. First order nociceptive fibers bring stimulus from nociceptors in the periphery to the spinal cord and release glutamate.

Question 30

Sympathetic outflow from the CNS to the eye follows which pathway:

Answer 30

Preganglionic fibers arising from the spinal grey matter through the ventral nerve root to the paravertebral ganglion, synapsing on postganglionic fibers to the eye

The sympathetic nervous system arises from spinal cord grey matter in the thoracic and lumbar spinal cord and course out through the ventral rami (like motor neurons) and synapse after a short distance on a paired bilateral paravertebral sympathetic ganglion chain.

Question 31

T/F?
Beta-1 activation also results in lipolysis (as well as Beta-3) and renin secretion in the kidney. Beta-2 activation results in bronchodilation, smooth muscle relaxation, and glycogenolysis (lysis of glycogen in the liver).

Answer 31

Beta-1 activation also results in lipolysis (as well as Beta-3) and renin secretion in the kidney. Beta-2 activation results in bronchodilation, smooth muscle relaxation, and glycogenolysis (lysis of glycogen in the liver).

Question 32

Sympathetic outflow results in:

A. Decreased anti-diuretic hormone release
B. Uterine contraction
C. Increased gastrointestinal sphincter tone
D. Increased salivation

What does sympathetic outflow do to GU sphincter tone?

Answer 32

Increased gastrointestinal sphincter tone

There was no way that we could allow sphincter tone be anything ‘butt’ the right answer. Ok, I’ll stop now. Sympathetic outflow results in increased ADH secretion (hang on to water/ intravascular volume), increased GI/GU sphincter tone and relaxation of GI/GU smooth muscle tone. It has variable effects on insulin secretion (beta-2 increases insulin secretion, alpha-2 decreases insulin). Salivation is increased with parasympathetic outflow.

Question 33

After release in the synapse, most of the norepinephrine is actively removed through reuptake mechanisms in ______.
Remaining norepinephrine is metabolized by _____.

Answer 33

Synaptic vesicles 
monoamine oxidase (MAO) and catechol O-methyltransferase (COMT).

Question 34

Thermoregulation and the inter threshold range:

Which drugs affect this?

Answer 34

Above the interthreshold range, there will be vasodilatation and sweating to cool the body. Below the interthreshold range there will be vasoconstriction and further down around 35.5 C, people will shiver. These processes are controlled in the hypothalamus, which results in an autonomic response.
But more than any of these factors, anesthetics can widen the range far more significantly. Anesthetics increase the sweating threshold moderately, and markedly decrease the cold-response thresholds. Volatile anesthetics do this to a greater extent than propofol. Opioids have a lesser effect.

Question 35

Theory of post-operative cognitive dysfunction-there are two. And is it in both general and regional anesthesia?

Answer 35

It has many theories, one of the most popular is that patients have a central cholinergic insufficiency due to anesthetics, opioids, sedatives, and of course, anticholinergics. Another theory you need to be aware of is anesthetic associated beta-amyloid phosphorylation, like that of Alzheimer’s disease.
POCD is far more common in the elderly and occurs with both general and regional anesthesia.

Question 36

Which of the following is NOT a risk factor for post-operative cognitive decline (POCD):

A. Hearing or visual impairment
B. Obesity
C. Duration of surgery
D. Tobacco use

Answer 36

B: Obesity

Obesity can confound POCD as rehabilitation and mobilization is delayed, but it’s not an overt major risk factor. By far the most significant risk factor is age, as well as type and duration of surgery. Other important risk factors are: any preexisting mental impairment or disease (including depression), substance use of any kind, low education, physical infirmary (so you could argue super morbidly obese), hearing and visual impairments, sleep deprivation, high ASA status, and male gender.

Question 37

Benefits of mild hypothermia intraoperatively include all of the following EXCEPT:

A. Decreased brain utilization of oxygen
B. Maintains ATP levels
C. Decreased post-operative morbidity
D. Preservation of phosphocreatine

Answer 37

C

Hypothermia, among other things, decreases neuronal oxygen demand while preserving energy sources (as evidenced by normal ATP and phosphocreatine levels). Therefore, remember that hypothermia will decrease cerebral metabolic rate and cerebral blood flow, but doesn’t improve outcome in brain surgery (most studied in humans is cerebral aneurysm surgery).