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Cerebral Blood Flow, Cerebral Spinal Fluid,

and Brain Metabolism

Part Two

Guyton Chapter 61

Morgan & Mikhail, 4th ed, Chapter 25

(or Morgan & Mikhail 5th ed, Chapter 26)

Blood Brain Barrier (BBB)• Cerebral blood capillaries are unique in that

the junctions between the vascular

endothelial cells are nearly fused (“tight-

junctions”)

• The fused endothelial walls constitute barriers

between the blood and the brain = Blood

Brain Barrier

Protects the brain from

sudden changes in osmolarity

or [electrolyte]

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Blood Brain Barrier (BBB)

• Movement of a substance across the BBB

governed by: size, lipid solubility, degree of

protein binding

– BBB allows easy passage of lipid-soluble

substances (CO2, O2, most anesthetics, ETOH) and

water into the brain

• Most ions (Na+, Cl-, H+, K+), proteins, and large

organic molecules (mannitol, glucose)

penetrate the BBB poorly

Blood Brain Barrier – the caveat

• Water moves freely XS BBB

• Movement of ions, glucose, mannitol impeded

• Rapid changes in [electrolyte] or [glucose]

produce osmotic gradients between plasma

and brain

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Blood Brain Barrier – the caveat

• Acute hypertonicity of plasma causes net movement of water out of the brain, while acute hypotonicity causes net movement of water into brain – when marked, these effects can cause rapid fluid shifts in the brain.

• Thus, marked abnormalities in serum Na+ or glucose should generally be corrected slowly.

Blood Brain Barrier

Disease disrupts BBB

CVA, head trauma, infection, toxins (CRF), severe HPTN,

seizure activity

�

Disrupt BBB

�

Increase access of drugs, toxins

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Meninges of the Brain3 membranes provide

protection to brain and spinal cord

1. Dura mater

2. Arachnoid mater

3. Pia mater

Essentially no barrier from CSF and brain

Arachnoid villi

Falx cerebri

Cerebral Spinal Fluid (CSF)

• Major function is to protect brain and spinal

cord against trauma

• Other functions of CSF:

– Regulate ECF environment of neurons

– Provide nutrition to neurons/neuroglia

– Carry products of metabolism (CO2) and

neurotransmitters away from nerves

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Cerebral Spinal Fluid (CSF)

• CSF is found within the ventricles of the brain,

in the cisterns around the brain, and in the

SAS surrounding the brain and spinal cord – all

theses chambers are connected to each other

• Normal CSF production = 21 mL/h (500

mL/day), yet total CSF volume = 150 mL

Cerebral Spinal Fluid (CSF)

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CSFChoroid plexuses of lateral ventricles

�

Interventricular foramina of Monro

�

Third ventricle

�

Cerebral aqueduct of Sylvius

�

Fourth ventricle

� �

Foramina of Luschka (2) Foramina of Magendi (1)

� �

Cisterna magna

� Most of the CSF is formed by choroid plexuses of the 4 cerebral

ventricles (mainly the 2 lateral ventricles)

� After circulating, CSF is absorbed into venous sinuses by

arachnoid villi or granulations – returning CSF to circulation

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Cerebral Spinal Fluid

• CSF compared with the plasma

– Isotonic

– ↓ Potassium

– ↓ Bicarbonate

– ↓ Glucose

– Essentially no protein

– Clear and colorless

– No blood cells

– Specific gravity = 1.005

Intracranial Pressure

(ICP)

Normal ICP = < 10 mmHg

S/S ↑↑↑↑ ICP:

headache, N/V

Cushing’s Triad (“CNS ischemic

response”)

• ↑ BP

• ↓ HR

• irregular

respiration

ICP is, by convention,

measured in the

subarachnoid space over

the cerebral cortex or in the

lateral ventricles

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Intracranial Pressure

• The cranial vault is a rigid

structure with a fixed

volume, consisting of:

– Tissue (80%)

– Blood (12%)

– CSF (8%)

Monroe-Kellie Doctrine ≡any increase in one component must be offset by an equivalent decrease in another to prevent a rise in ICP.

� ICP is normally

regulated by absorption

of CSF into the arachnoid

villi, which act as

“pressure valves” that

open when the ICP

increases

↑ Intracranial Pressure

Compensatory

Mechanisms

1. Initial displacement of

CSF from cranium →

spinal compartments

2. ↑ CSF absorption

3. ↓ CSF production

4. Displacement of

cerebral blood volume

Treatment

– Mannitol 0.25-1.0

g/kg

– Loop diuretics (Lasix

IV, 0.5-1 mg/kg)

– Head-up 30°

– Control BP

– Hyperventilate

– Restrict fluids

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Cerebral Perfusion Pressure (CPP)

Moderate to severe increases in ICP (>30 mmHg) can significantly compromise the CPP and CBF, even in presence of normal MAP

CPP = MAP - ICP

Normal CPP = 60-110

mmHg

Cerebral Perfusion Pressure

CPP = MAP - ICP

• If CVP > ICP, substitute CVP in equation

• Adequate CPP usually maintained with MAP > 60T

• CPP < 50 T = EEG slowing

• CPP < 25 T = irreversible damage

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Cerebral Perfusion Pressure and

Patient Position• MAP at base of brain

15-20 mmHg lower

than arm

• Another 9 mmHg lower

at top of brain

• e.g. MAP at arm = 90

mmHg; MAP at cerebral

cortex = 65 mmHg

• 1 mmHg ↓ in MAP for

every 1.25 cm above

the heart

Cerebral Dynamics - anesthesia

• Luxury perfusion is the combination of ↓ neuronal metabolic demand and ↑ CBF associated with volatile anesthetics

• These effects may be desirable during induced hypotension or cases that ↑ the risk of global ischemia

• Barbiturates and hyperventilation (↓CO2) cause vasoconstriction in normal or healthy areas of the brain. Blood flow is shunted from healthy to diseased areas, a process called the Robin Hood effect or reverse steal or inverse steal

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Cerebral Dynamics - anesthesia

• In contrast to their potentially beneficial effect during global ischemia (luxury perfusion) circulatory steal (intracerebral steal) is possible with volatile anesthetics in the setting of focal ischemia.

• Volatile agents (also hypercarbia, NTG, NTP) increase blood flow in normal areas of the brain, but not in ischemic areas, where arterioles already are maximally vasodilated (ischemic vasomotor

paralysis). This may result in redistribution of blood flow away from ischemic to normal areas.

Volatile Inhalational Agents

– Isoflurane

– Desflurane

– Sevoflurane

• all ↑ CBF and ICP

• all ↓ CMRO2

• CO2 responsiveness preserved

• autoregulation impaired in dose-

dependent manner

Opioids • minimal effects on CMRO2, CBF,

and ICP

• autoregulation preserved

• CO2 responsiveness preserved

IV Anesthetics

– Barbiturates

– Propofol

– Etomidate

– Ketamine

• all ↓ or have minimal effects on

ICP, except for Ketamine

• all ↓ or have minimal effects on

CBF, except for Ketamine

• autoregulation preserved

• CO2 responsiveness preserved

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Brain Metabolism

• CMRO2– CMRO2 = 50 ml/min; constitutes 20% of body’s total O2

consumption

– The metabolic rate of the brain is 7X average BMR in body

– Most of the metabolism used to generate ATP for Na/K+ pumps; each time neuron conducts AP, RMP must be restored

– Seizures ↑↑ CMRO2

• Obligate Requirement for O2– Neuronal activity has second-by-second requirement for

O2 to generate sufficient ATP

Brain Metabolism

• Glucose for brain energy

– Under nl conditions, glucose supplies almost all of brain’s energy requirements – exception starvation

– Brain accounts for 50-70% of the body’s total glucose consumption - 5-10 mg/100 gm/m (about 150 gm/day)

– Acute, sustained hypoglycemia equally as devastating as hypoxia

– Special feature: transport of glucose into the neuron not dependent on insulin

• Paradoxically, hyperglycemia can exacerbate brain injury associated with global and focal ischemia → accelerates cerebral acidoisis and cellular injury *** avoid dextrose containing solutions in normoglycemic patients with brain injury

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Brain Protection

• Hypothermia

• Barbiturates

• Methylprednisolone

• Avoid hyperglycemia

• Maintain normocarbia

• Maintain O2 carrying capacity

• Maintain normal or slightly increased BP