CSF and ICP Flashcards

1
Q

What is the Munro Kellie Doctrine

A
  • It is determined by the three components of the Monro-Kellie relationship, which states that an increase in the volume of one intracranial compartment will lead to a rise in ICP unless it is matched by an equal reduction in the volume of another compartment
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2
Q

Draw an intracranial pressure volume vurve

A
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3
Q

What is the 3 volume s of the compartments making up the Munro Kellie doctrine

A

◦ Brain tissue: 1400ml on average
◦ Cerebral blood volume: 150ml
◦ Cerebrospinal fluid: 150ml

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4
Q

What is a normal ICP? How does it vary with position?

A
  • Normal ICP 7-15mmHg or <20mmHg
    ◦ On average 9mmHg across 24 hours
    ◦ Head down 14-19mmHg
    ◦ With heads lifted 20 degrees the ICP was 3-4mmHg
    ◦ Interestingly if someone is totally upright variation can be -2 to +2
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5
Q

CSF pressure = (equation)

A

CSF pressure = resisatnce to CSF outflow x CSF formation + pressure in sagittal sinus

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6
Q

What is CSF production dependent on

A

CPP (not ICP

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7
Q

How is CSF production related to ICP

A

It is related to CPP

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8
Q

What is the normal variation in the the ICP trace due to?

A
  1. percussion
  2. Tidal
  3. Dicrotic
  4. Respiratory
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9
Q

What are the names for P 1-3 on the ICP trace

A
  1. percussion
  2. Tidal
  3. Dicrotic
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10
Q

What does increased amplitude of all waves indicate

A

Increased CSF volume
Missing bone flap

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11
Q

What does diminished P1 indicate

A

Reduced CPP

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12
Q

Prominent P1 menas

A

Systolic BP too high

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13
Q

Prominent P2

A

Oedema - reduction in cerebral compliance

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14
Q

How does ICP change with posture

A
  • Intracranial pressure is normally ~ 10 mmHg in the supine person, and probably 0-2 mmHg in the upright person
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15
Q

How is ICP regulated 3

A
  1. Displacement of venous blood out of the CNS
  2. Displacement of CSF out of the CNS - to the psinal cord, venting to veinous circulations
  3. Meningeal distension
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16
Q

What is the most important minute to minute ICP regulation mechanism

A

Displacement of veinous blood out fo CNS

◦ Displacement of venous blood out of the CNS - large and mobile component, and can shift at short notice
	‣ Arterial volume is smaller and higher pressure so shfits in it are of less significance 
	‣ Venous displacement likely accounts for the majority of second to second changes
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17
Q

What are the 2 ways CSF can be displaced from the cranium due to raised ICP?

A
  1. Into spinal cord due to better compliance
  2. Venting to veinous circulation - low velocity
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18
Q

What are factors affecting ICP

A
  1. Munro Kellie doctrine assumptions - that you have an intact cranial vault - sometimes not true
  2. CSF volume
    - CSF production
    - VSF drainage
  3. Arterial and veinous volume
    - Arterial - cerebral metabolic rate, vasoactive agents, systemic
    - Veinous - outflow obstruction either pressure or physical obstriction
  4. Brain - blood, tumour
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19
Q

How can CSF efflux be affeted

A

eg. hydrocephalus, EVD, VP shunt)
‣ ability to drain the CSF –> into the spinal cord inthe case of hydrocephalus, out of the CNS in EVD, VP shunt or inadvertant dural tear or into the venous ciruclation when arachnoid granulations are occluded by meningitis or SAH

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20
Q

Why might CSF production be reduced

A

(acetazolamide, diuretics, dehydration)
‣ CSF production directly
‣ Reduced volume status

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21
Q

What factors affect brain volume

A

◦ Age (decreased mass)
◦ Space occupying lesions (eg. tumour, abscess)
◦ Cerebral oedema

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22
Q

What 3 factors affect arterial brain volume

A

◦ Arterial blood volume
‣ Cerebral metabolic rate (eg. hyper or hypthermia, seizures, sedation)
‣ Cerebral arterial vasoactive agents (CO2, hypoxia)
‣ Systemic increases in blood flow or blood pressure (eg. pain, anxiety)

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23
Q

What 2 factors affect veinous volume

A

◦ Venous volume
‣ Venous outflow obstruction (eg. raised intra-thoracic pressure (valsalva, cough, childbirth), shivering, coughing, C-spine collar, jugular or sinus venous thrombosis, poor RV compliance
‣ Venous reflux - head down
‣ Venous efflux - upright

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24
Q

Mechanisms of agents used to reduce ICP are 34

A
  1. Cerebral metabolic demand
    - Sedation
    - Seizure
  2. Improve veinous flow - reduced cough, muscle realxant, diuretic
  3. Reduce brain tissue volume - osmotherpay, dexamethasone
  4. CSF production - Acetazolamide inhibits carbonic anydrase
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25
Q

What are the 2 drugs that can reduce brain volume

A

Dexamethasone
Osmotic therapy

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26
Q

5 methods of measurnig ICP

A

CLinical
EVD
Codman
Epidrual catheter
Lumbar puncture

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27
Q

What is CSF

A

ultrafiltrate of plasma contained within the ventricles of the brain and the subarachnoid spaces of the cranium and spine.

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28
Q

How much CSF is produced per day

A

25ml/hr
400-600ml per day

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29
Q

How much CSF do you have at any one time

A

150ml

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30
Q

How is CSF distributed

A

25ml ventricles
30ml in spinal cord
remaining in subarachnodi space

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31
Q

What are the 3 sources of CSF production

A

CHoroid plexus in lateral ventricles 75%
Brain intersitial fluid - brain cpaillaruy endothelial cells
Circumventricular organ

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32
Q

How is CSF produced

A

Highly regulated ultrafiltration and secretion

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33
Q

How is there an ultrafiltrate when there is a BBB

A
  • Ultrafiltrate of plasma is formed by the fenestrated choroidal capillaries
    ◦ The choroid plexus is the highest surface area of BBB fenestration and the largest fluid output area for CSF
    ◦ lack tight junctions
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34
Q

What determines the fluid in the intersitial space within the choroid

A

Starlings forces

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35
Q

How is the intersitial space of the choroid translated to CSF?

A

CHoroidal epithelium

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36
Q

Choroidal epithelium histological feature

A

Microvilli in the ventricle

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37
Q

How is the ionic content of the CSF regualted

A
  1. Na - actively secreted from apical membrane + Sodium co transport with Cl
  2. Carbonic anhydrase provides H+ to power Na/H+ exchange at basal membrane and makes HCO3 for transport into the CSF
  3. Cl/HCO3 exchanger
  4. Na/K/2Cl cotransporter
  5. Aquaporins then allow water to flow transcelluarly in basal and apical membrane
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38
Q

How is sodium transported in the CSF?

A
  1. Na - actively secreted from apical membrane + Sodium co transport with Cl
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39
Q

How is carbonic anhydrase involved in CSF production

A
  1. Carbonic anhydrase provides H+ to power Na/H+ exchange at basal membrane and makes HCO3 for transport into the CSF

The HCO3 is then exchanged for Cl

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40
Q

How does water cross into the CSF

A

Aquaporins then allow water to flow transcelluarly in basal and apical membrane

Flow down the gradient created by ionic transport

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41
Q

CSF production vs pressure

A

Pressure independnet unless CPP <55mmHg and then it decreases

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42
Q

Describe the cation content of CSF with reference to plasma?

A
  • CSF sodium potassium and calcium are slightly lower than plasma
    ◦ Calcium lower due to less albumin, ionised calcium similar, tihgtly regulated
    ◦ Tightly regulated CSF K to be slightly lower to not interfere with transmembrane gradient, independent of blood K - 2.9 mmol/L
    ◦ Sodium varies with plasma levels, activity is essentially the same 135-140
    Ca 1.12mmol/L
    Mg 1.1mmolL
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43
Q

When descibring CSF content what are the 6 domains

A
  1. Cations
  2. Anions
  3. Acid base
    4, Cells
  4. Protein - total protein and specific beta 2 transferrin
  5. Glucose
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44
Q

How does sodium activity in the CNS compare with plasma for osmolality?

A

Similar
Level is very slightyl lower 135-140mmol/L

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45
Q

How does CSF anion concentration vary compared to plasma

A
  • CSF chloride, CO2 and bicarbonate are higher than plasma
    ◦ Higher bicarbonate - no proteins to act as buffers, it is exactly what you’d expect from the Henderson/Hasselbach equation
    ◦ Chloride - main anionic proteins not present therefore maintain electroneutrality; 15-20mmol higher (124mmol/L)
46
Q

What is the bicarbonate content of CSF

A
  • CSF chloride, CO2 and bicarbonate are higher than plasma
    ◦ Higher bicarbonate - no proteins to act as buffers, it is exactly what you’d expect from the Henderson/Hasselbach equation
    ◦ Chloride - main anionic proteins not present therefore maintain electroneutrality; 15-20mmol higher
47
Q

What is the protein content in CSF?

A
  • CSF contains minimal protein (~0.2g/L)
    ◦ With intracranial bleeding for every 100RBC you get a 0.01g/L increase in protein
    ◦ Reasons for raised protein
    ‣ Exudation – infection (menginitis, enecephalitis), malignancy through immature capillaries, mycobacterial infection
    ‣ Increased portein due to local synthesis - neurosyphillis, MS, sarcoidosis, infection
    ‣ Decreased reabsorption - hydrocephalus
48
Q

Why might CSF protein be raised

A
  • CSF contains minimal protein (~0.2g/L)
    ◦ With intracranial bleeding for every 100RBC you get a 0.01g/L increase in protein
    ◦ Reasons for raised protein
    ‣ Exudation – infection (menginitis, enecephalitis), malignancy through immature capillaries, mycobacterial infection
    ‣ Increased portein due to local synthesis - neurosyphillis, MS, sarcoidosis, infection
    ‣ Decreased reabsorption - hydrocephalus
49
Q

CSF glucose vs plasma glucose

A
  • CSF glucose is about 2/3rds of the plasma value
    ◦ 2-4mmol/L range, tracks BSL but lags by 2-4 hours
    ◦ Its lower value does not correspond to brain metabolism
    ◦ Causes of low CSF glucose
    ‣ Bacterial meningitis
    ‣ Viral meningitis - often normal
    ‣ IC malignancy
    ‣ CNS sarcoidosis
    ‣ SAH - RBC consume glucose

It passes across due to faciliated diffusion

50
Q

Why might CSF glucose be low

A
  • CSF glucose is about 2/3rds of the plasma value
    ◦ 2-4mmol/L range, tracks BSL but lags by 2-4 hours
    ◦ Its lower value does not correspond to brain metabolism
    ◦ Causes of low CSF glucose
    ‣ Bacterial meningitis
    ‣ Viral meningitis - often normal
    ‣ IC malignancy
    ‣ CNS sarcoidosis
    ‣ SAH - RBC consume glucose
51
Q

How does pH compare between blood and brain

A
  • pH slightly lower - but must remain similar to the blood as the pH of cerebral interstitial fluid is what central chemoreceptors sample. It will change with plasma PCO2 (pH7.33)
    ◦ Explains changes in ventilation in meningitis
    ◦ It is lower as PCO2 is higher by 4-11mmHg as there is no haemoglobin or protein to buffer (no Bohr/Haldane effect) and more closely resembles venous blood
52
Q

Why is there a difference in PCO2 in the brain compared to the blood? What impact does this have?

A
  • pH slightly lower - but must remain similar to the blood as the pH of cerebral interstitial fluid is what central chemoreceptors sample. It will change with plasma PCO2 (pH7.33)
    ◦ Explains changes in ventilation in meningitis
    ◦ It is lower as PCO2 is higher by 4-11mmHg as there is no haemoglobin or protein to buffer (no Bohr/Haldane effect) and more closely resembles venous blood

pCO2 50

53
Q

What is the CSF WCC to RBC ratio allowed

A

1:500

54
Q

What si the normal leucocyte count in the CSF

A

<3
CSF pleocytosis not uncommon with EVDs
4-5 RBC per mL

55
Q

What are the 4 functions of CSF?

A
  • Barrier function (the blood-CSF barrier)
    ◦ Shields neural tissue from unregulated exposure to substances - large proteins, bacteria and virus particles, neurotransmitters, hormones and metabolic toxins
  • Chemical stability and waste removal of extracellular environment inc. pH
    ◦ Maintains concentration gradient for removal of waste products and electrolytes and interstitial fluid transit through perivascular spaces would be inefficient
  • Buoyancy and mechanical cushioning of the CNS
    ◦ Average brain mass 1400g, net weight while suspended in fluid is 50g
    ◦ Ventricles are particualrly effective for this byoyancy as they are a low density bubble of variable volume quickly buffering changes in brain density
  • Hydraulic pressure buffering of ICP with arterial pulse and respiration
    ◦ Compensating for raised ICP
    ◦ Transient changes displace CSF into the spinal canal, and sustained changes increase reabsorption
    ◦ Arterial pulse causes a 1-2mmHg fluctuation in lumbar CSF pressure
56
Q

4 functions of CSF

A
  1. Hydraulic pressure buffering
  2. Buoyancy
  3. Shielding from toxic substances
  4. Removal of waste proudcts
57
Q

Describe how buoyancy of the brain is facilitated

A

◦ Average brain mass 1400g, net weight while suspended in fluid is 50g
◦ Ventricles are particualrly effective for this byoyancy as they are a low density bubble of variable volume quickly buffering changes in brain density

58
Q

What is the path of circulation of CSF

A
  1. CHoroid plexus
  2. Lateral ventricle –> 3rd ventricle via foramen of munro
  3. 3rd ventricle
  4. Cerebral aqueduct (Acqueduct of Sylvius)
  5. 4th Ventricle
  6. Foramen of Magendie and Lushka
  7. Subarachnoid space - basilar cisterns via the Sylvian fissure to cortial regions or to the spinla subarachnoid space via central canal
59
Q

What is the join between the lateral ventricles and the 3rd ventircle called

A

foramen of munro

60
Q

WHat is the joint between the 3rd and 4th ventricle called

A

cerebral aqueduct of sylvius

61
Q

What drives CSF reabsorption

A
  1. Arterial pulsation pressure
  2. Constant production
  3. Venous pulsatino and varation in pressure

Essentially hydrostatic pressure differences - ultrafiltration - it is pressure dependent and relies on CSF pressure 1.5mmHg greater than veinous pressure

62
Q

How fast is CSF reabsorbed

A

25ml/hr

63
Q

Where is CSF reabsorbed

A

85% via arachnoid granulations in dural veinous sinuses - outpouchings of arachnoid space through the dura into sagital and sigmoid sinuses. Mostly via pinocytosis and opeing of extracellualr fluid spaces, and pressure dependent

Ventricle walls
Cervical lymphatics

64
Q

When does CSF reabsorption stop

A

CSF pressure ~7cmH20

65
Q

Baseline cerebral blood flow is what % anterior and what % posterior

A

70/30

66
Q

How much blood does the brain get in mls/min and as a % of cardiac output

A

15% cardiac output
750ml/min

67
Q

What is the blood supply to the brain in ml/100g/min

A

50ml/100g/min

68
Q

How much does a brain usually weigh

A

1400g

69
Q

What si the DO2/VO2 supply to the brain at baseline

A

3:1

70
Q

What is the equation used to describe determinants of cerebral blood flow

A
  • It is described by the Ohm equation, Q = (Pa- Pv) / R, where
    ◦ (Pa- Pv) is the cerebral perfusion pressure (CPP) - use CVP or ICP whichever is higher
    ◦ R is the cerebral vascular resistance
    ◦ As Ohm’s law reflects: pressure is the product of resistance and flow
71
Q

Cerebral resistance can be described using what equation? How does it compare to other areas of the body?

A
  • Cerebral resistance (R) = (8 l η) / πr4, where
    ◦ l = length of the vessel
    ◦ η = viscosity of the blood - excess of cells or protein
    ◦ r = radius of the cerebral vessels, which is the main variable susceptible to regulation
    ◦ The cerebral resistance is very low compared to other organs
72
Q

Define cerebral autoregulation

A
  • Cerebral autoregulation is a homeostatic process that regulates and maintains cerebral blood flow (CBF) constant and matched to cerebral metabolic demand across a range of blood pressures.
73
Q

What are the mechanisms by which cerebral autoregulation likely occurs

A

◦ Autonomic neurogenic theory - cerebral vessels have rich autonomic innervation so it must play a role in vascular control; cannot be the only mechanism as present with denervation
◦ Endothelial mechansism - pressure stretch or shear on endothelium lead to paracrine mediators producing vasodilation
◦ Myogenic autotegulation
◦ Metabolic autoregulation - CO2, pH, lactate, potassium, low oxygen, adenosine, nitric oxide

74
Q

What range of MAP is CBF stable over

A

MAP 50 -150

75
Q

Draw a graph illustrating the concept of cerebral autoregulation. Include how PaO2 and PaCO2 influence this

A
76
Q

Illustrate on a Cerebral blood flow graph how PCO2 influences flow

A
77
Q

At what range of PCO2 does autoregulation become severely impaired in humans

A

55-60 anaesthetised

78
Q

What does raised PCO2 affect in autoregulation

A

Autoregulation plateau shrinks and the baseline cerebral blood flow increases 1-2ml/100g/min for every 1mmHg rise in CO2

79
Q

How much does a rise in CO2 affect cerebral blood flow

A

1-2ml/100g/min for every 1mmHg rise in CO2

Such that by the time PCO2 is 80 cerebral blood flow has doubled (maximum dilation)

80
Q

What si the maximal vasoconstriction that can be induced with hypocapnoea

A

PCO2 20 –> 40% drop in blood flow

81
Q

What si the pharmacodynamcis for CO2 influencing cerebral blood flow?

A

‣ Reduction in pH due to high CO2 tension
‣ Nitric oxide synthase activity increases–> increases intracellular cGMP production
‣ cGMP acts as a secondary mecahnism to affect a change in intracellular calcium availability
‣ Decreased cerebral vascular resistance is the result

82
Q

How does blood flow change with hypoxia?

A

PaO2 falling below 50 mmHg leads to exponentially increased CBF
◦ Stable linear relationship of BP in hyperoxia and normoxia, only at around 50mmHg PaO2 does cerebral vascular resistance drop and from here cerebral blood flow increases exponentially

83
Q

Draw a graph to illustrate the relationship of cerebral blood flwo to oxygenation

A
84
Q

What are the 5 factors influencing cerebral blood flow

A

PaO2
PaCO2
Temperature
Medications
MAP

85
Q

Temperature affects cerebral metabolic rate how?

A

For every 1 degree fall in body temperature CMRO2 decreases by 7%

86
Q

How does propofol affect CMRO2

A

Effects of propofol on cerebral blood flow and CMRO2:
* Propofol produces a dose-dependent decrease in CMRO2.
* As CMRO2 is closely tied to the autoregulation of blood flow, it also decreases CBF
* The relationship between CBF and CMRO2 changes is linear
* Thus, because both oxygen consumption and oxygen delivery are decreased together, the total oxygen extraction ratio remains stable, and there is no change in the SjvO2 (Oshima et al, 2002)

87
Q

How does ketamine influence cerebral blood flow

A
  • Ketamine certainly increases CBF
  • Ketamine supposedly also increased CMRO2.
  • The increase in CBF is said to be in excess of the increase in metabolic rate (
  • Therefore, ketamine decreases SjvO2
88
Q

Define BBB

A
  • The blood brain barrier is a diffusion barrier which impedes influx of most compounds from blood to brain.
89
Q

What are the layers of the BBB

A

Endothelial cells with tight junctions
Basement membrane
Pericytes (supportive tissue)
Perivascular fluid space
Astrocyte foot processes

90
Q

How do endothelial cells function as an element of the BBB (4)

A
  1. Tight junctions - impermeable to water (occludin and adherin)
  2. No fenestrations - continuous lipid bilayer
  3. Metabolism - MAO, cholinesterase
  4. efflux pumps - ABC transporter, P glycoprotein
91
Q

What are the signficant features of the basement membrane of basal lamina of the BBB

A

20-30nm wide
Collagen containing and laminins
Scaffold structure

92
Q

Perivascular fluid space in BBB is also known as?

A

Virchow Robin sapce

93
Q

Describe the anatomy of the perivascular fluid space of the BBB

A

◦ Fluid filled cavity separating the astrocyte foot processes from the smooth muscle of arterioles as they course into the brain tissue
◦ potentially clearage spaces fro metabolic waste
◦ There are pial fenestrations allowing communication between intersititum and CSF

94
Q

What is the main supportive cell of the BBB outside the cpaillary

A

Astrocyte foot processes

◦ Relatively non essential from a functional BBB perspective but likely form some regulator function and assist in development of the BBB in the first place
95
Q

What do the tight junctions in the BBB prevent

A

Passage of hydrophilic molecules

96
Q

What are the non barrier mechanisms that the BBB utilises to form a further barrier

A
  1. Drug metabolism within cells e.g. dopa decarboxylase in endothelial cells
  2. Drug efflux pumps e.g. P glycoprotein
97
Q

What are the mechanisms of transport across the BBB

A
  1. Paracellular transport - usually limited
  2. Passive transport of small lipophilic molecules
  3. active facilitated diffusion e.g. vitamins, peptides
  4. Specific active transport
98
Q

What glucose transport proteins are present on BBB

A

Glut 1 and 3

99
Q

What factors are actively transported at the bBB

A

◦ Glut1and Glut 3
◦ MCT famiyl of monocarboxylic AA transporters - Short chain fatty acid, salicylic acid, biotin, lactate and valproate
◦ AA transporters - aspartate, glutamate, lysin, arginine, L ornithine
◦ Choline transporters - choline and thiamine
◦ Peptide
◦ Nucleoside

100
Q

What are ideal characteristics of a drug to penetrate the BBB

A
  • Passive transport
    ◦ Small molecular weight - facilitating diffusion
    ◦ High lipophilicity e.g. propofol
    ◦ Low polarity
    ◦ Low volume of distribution - high blood concentration
    ◦ High concentration gradient (low protein binding, small volume of distribution, low potency of drug i.e. large concentration of drug)
  • Hydrophilic drugs
    ◦ Hgh concentration gradient - forces it paracellularly e.g. ethanol
    ◦ Low protein binding - large free fraction
101
Q

How do hydrophilic drugs penetrate the BBB

A
  • Hydrophilic drugs
    ◦ Hgh concentration gradient - forces it paracellularly e.g. ethanol
    ◦ Low protein binding - large free fraction
102
Q

What are examples of drugs which utilise active transport by impersonating normal drugs?

A

Lithium (sodium)
Valproate (lactate)

103
Q

Where is the BBB interrupted 5

A
  1. Area postraema - CTZ
  2. CHoroid plexus
  3. Pineal gland
  4. Posterior pituitary
  5. Hypothalamic centres - Preoptic recess of anterior hypothalamus, osmoreceptors within hypothalamus (lamina terminalis)

Organ vasculosum lamina terminalis
Subfornical organ
Medial eminence

104
Q

What is the name of the area that acts as CTZ? Where is it located

A

Medulla on the floor of the 4th ventricle

105
Q

What connections closely reside next to the CTZ

A

NTS
Motor dorsal vagal nucleus

106
Q

Where is the choroid plexus primarily

A

◦ Several areas of CSF secreting tissue in the psoterior horns of the lateral ventricles and roof ot eh 3rd and 4th ventricles

107
Q

Pineal gland does what

A

◦ Endocrine organ between halves of the thalamus, secretes melatonin into systemic circulation
◦ Fenstrated capillaries facilitate direct entry of melatonin

108
Q

What is the OVLT

A

Organam, vasculosum lamina terminalis - circumventricular organ with sensory role in osmoreceptors

109
Q

What are the 4 circumventricular organs? Where are they located? What do they communicate with

A

The vascular organ of lamina terminalis (VOLT), organum vasculosum of the lamina terminalis (OVLT), or supraoptic crest is one of the four sensory circumventricular organs of the brain, the others being the subfornical organ, the median eminence, and the area postrema in the brainstem

Communicate with the hypothlamus for sodium and osmolality control

Located around the 3rd ventricle

110
Q

What is baseline cerebral blood flow?

A

750ml/min 14% CO
50ml/100g/min

111
Q

What is the effect of CO2 and O2 on cerebral blood flow

A

PaCO2: ­ in CBF linearly by 1-2ml/100g/min for every 1mmHg ­ in PaCO2 over range 20-80mmHg

PaO2 < 50mmHg à CBF increases non-linear (exponential)

112
Q
A