Brain Metabolism

Question 1

compensation for additional volume in the skull

Answer 1

-increased CSF drainage
-increased venous drainage

once these compensatory mechanisms are exhausted, we experience rising intracranial pressure

Question 2

brain compliance

Answer 2

*relationship between intracranial pressure and volume
*as intracranial volume increases, intracranial pressure also increases
*ICP increases slowly due to compensatory mechanisms, but once those mechanisms are exhausted, ICP increases rapidly, leading to decreased CPP (cerebral perfusion pressure) and herniation risk

Question 3

treatments for increased ICP

Answer 3

-elevate head of bed
-HYPERventilate patient
-osmotic agents (mannitol, hypertonic saline)
-steroids for vasogenic edema (tumors)
-heavy sedation
-surgical options (ventricular catheter to drain ICP; hemicraniectomy)
-avoid hypoxia (low paO2), hypercarbia (high paCO2)
-adequately treat pain, fever, and seizures

Question 4

cerebral perfusion pressure (CPP) =

Answer 4

CPP = MAP - ICP
*note: in normal people, ICP is < 15, so CPP is only slightly lower than MAP in someone with normal ICP
*if ICP gets too high, it severely limits your ability to perfuse the brain tissue and it starts to die

Question 5

hyperventilation as treatment for increased ICP

Answer 5

*hyperventilation leads to decreased paCO2
*decreased paCO2 leads to respiratory alkalosis
*respiratory alkalosis leads to VASOCONSTRICTION of intracranial arteries
*vasoconstriction REDUCES cerebral blood flow and cerebral volume

*NOTE: hyperventilation works fast but is only temporary, as a short-term bridge to more definitive therapy [because prolonged decrease in CBF can produce ischemia]

Question 6

should you hyperventilate or hypoventilate a patient with elevated ICP

Answer 6

HYPERventilate them (leads to decreased paCO2 to respiratory alkalosis to vasoconstriction to reduced CBF)

Question 7

what happens if you hypoventilate a patient with elevated ICP

Answer 7

*hypoventilation causes CO2 retention, leading to higher paCO2, leading to respiratory acidosis, leading to arterial vasodilation, aggravating the high ICP

Question 8

cerebral blood flow equation

Answer 8

CBF = (CPP * (radius of blood vessel^4) * pi) / (blood viscosity * length of blood vessel)

*blood vessel RADIUS is the key factor for determining CBF

Question 9

what is the key factor for determining cerebral blood flow (CBF)

Answer 9

RADIUS of blood vessels

-increased radius (dilated vessel) = increased cerebral blood flow = increased ICP (BAD if a patient has elevated ICP)
-decreased radius (constricted vessel) = decreased cerebral blood flow = decreased ICP (GOOD if patient has elevated ICP)

Question 10

brain metabolism - oxygen and glucose consumption relative to mass of body

Answer 10

*brain weighs ~2% of body weight
*uses glucose as primary energy source
*uses 20% of total oxygen and 25% of total body glucose consumption!
*receives 15-20% of cardiac output at rest

Question 11

what is the average cerebral blood flow

Answer 11

50cc per 100 grams of brain tissue per minute

Question 12

which is more metabolically active: gray matter or white matter?

Answer 12

*GRAY matter is more metabolically active
*so, gray matter requires more cerebral blood flow on average than white matter
*so, gray matter is more susceptible to damage with changes in CBF

Question 13

penumbra

Answer 13

*REVERSIBLE neuronal damage (at risk brain tissue)
*occurs when cerebral blood flow is ~15-20 cc/100g/min
*will become infarction with passage of time

Question 14

irreversible neuronal damage

Answer 14

*occurs when the cerebral blood flow is below ~10-15cc/100g/min

Question 15

factors that influence cerebral blood flow

Answer 15

-local neuronal activity
-autoregulation
-raised ICP
-paCO2
-paO2
-hematocrit
-temperature
-autonomic regulation

Question 16

synthesis and storage of glycogen in the brain occurs primarily in ?

Answer 16

*in astrocytes!

-much smaller amount of glycogen in brain than other organs
-acts as an energy buffer
-would last only a few minutes if glycogen was used exclusively

Question 17

important glucose transporters in the brain

Answer 17

*GLUT1 and GLUT3
*both are required for transport across the blood-brain barrier
*GLUT1 is primarily in astrocytes and endothelial cells
*GLUT3 is primarily in neurons

Question 18

neurovascular coupling

Answer 18

*aka flow-metabolic coupling or functional hyperemia
*purpose = increase blood flow to active areas of brain
*supplying necessary oxygen and glucose to regions of high neuronal activity!

Question 19

how are vasoactive changes in the brain mediated by neurons and astrocytes to regulate cerebral blood flow

Answer 19

*glutamate is a significant regulator of CBF
*other molecules (hydrogen, potassium, adenosine, etc) also mediate blood flow changes
*result = vasoconstriction or vasodilation of intracranial blood vessels to regulate CBF

Question 20

resistance vessels

Answer 20

*branches of cerebral arteries that run along the SURFACE of the brain
*smooth muscle cells lining the arteries respond to changes in ICP and vasoactive mediators to cause changes in blood vessel diameter
*resistance vessels include: penetrating arterioles, capillaries, venules, and pial arterioles

Question 21

autoregulation - general concept

Answer 21

*brain maintains constant cerebral blood flow, despite fluctuations in CPP (cerebral perfusion pressure) or MAP (mean arterial pressure) by CHANGING CALIBER (diameter) OF PIAL ARTERIOLES

Question 22

how is cerebral blood flow impacted by chronic hypertension

Answer 22

*people with a chronically high MAP require a higher CPP to start the autoregulation cascade in order to maintain CBF
*essentially, curve is shifted to the right because there is a higher set point for autoregulation to occur
*can tolerate higher perfusion pressures

Question 23

what ranges of MAP is autoregulation good for

Answer 23

*autoregulation works well for MAP 60-150 mmHg
*outside this range, CBF varies DIRECTLY with perfusion pressure
*loss of autoregulation can be focal or global in brain injury

Question 24

what happens if MAP or CPP drop too low (in people with intact autoregulation)

Answer 24

vessels cannot dilate any further to compensate, leading to ISCHEMIC INJURY

Question 25

what happens if MAP or CPP become too high (in people with intact autoregulation)

Answer 25

*high pressure inside vessels overcomes maximal constriction, so BBB is disrupted
*this leads to HYPERPERFUSION, causing cerebral edema +/- hemorrhage

Question 26

impact of paCO2 on cerebral blood flow

Answer 26

*decreased paCO2 (hyperventilation) -> vasoconstriction -> decreased CBF

*increased paCO2 (hypoventilation) -> vasodilation -> increased CBF

**OVERALL: CBF varies DIRECTLY with paCO2 in physiologic range

Question 27

impact of paO2 on cerebral blood flow

Answer 27

*low paO2 (< 60 mmHg) = trigger to increase CBF (vasodilate) to maintain O2 delivery
NOTE: paO2 is not as impactful as paCO2 on cerebral blood flow

Question 28

ways to evaluate CBF and cerebral metabolism

Answer 28

-transcranial doppler (TCD)
-positron emission tomography (PET)
-CT perfusion
-MR perfusion with pulsed arterial spin labeling (PASL)
-cerebral microdialysis
-functional MRI (fMRI)
-Tc-99m radionuclide study

Question 29

transcranial doppler (TCD)

Answer 29

*ultrasound measurement of blood flow velocities in major vessels
*can evaluate for autoregulation by manipulating paCO2

Question 30

positron emission tomography (PET)

Answer 30

evaluates cerebral metabolism (usually glucose uptake)

Question 31

CT perfusion

Answer 31

evaluates blood flow, volume, and mean transit time to look for penumbra (at-risk brain tissue)

Question 32

MR perfusion with pulsed arterial spin labeling (PASL)

Answer 32

shows cerebral perfusion

Question 33

cerebral microdialysis

Answer 33

evaluates cerebral metabolism by measuring local metabolites

Question 34

functional MRI (fMRI)

Answer 34

uses blood oxygenation level dependent (BOLD) imaging to evaluate regional differences in CBF based on activity

Question 35

Tc-99m radionuclide study

Answer 35

*assess flow of radio-tracer to assess CBF
*can be used to evaluate for brain death