1. Central nervous system physiology
and cerebral blood flow
Prepared dr tam weiyaw
Supervisor DR WAN NAZA

2. Blood supply of the brain…
• Derived from 2 internal carotid and 2 vertebral arteries which lie in
the subarachnoid space
• Two thirds of the brain is supplied by the internal carotids.
- they ascend through the carotid canal in the petrous temporal
bone ; enter the skull where they have tortuous course, ending by
dividing into the anterior & middle cerebral arteries.
• The anterior cerebral artery :
- supply the superior and medial parts of the cerebral
hemisphere
- Linked by the ant communicating artery, making the
anterior portion of the circle of willis.

3. • The middle cerebral arteries supply most of the lateral side
of the hemisphere, and branches supply the internal
capsule.
• The blood supply to the other one third of the brain comes
from the vertebral arteries.
- branches from the subclavian artery.
- ascend in the transverse foramina of the upper
six cervical vertebrae and enter the skull by
piercing the dura @ the foramen magnum

4. - they run on the medulla and join in front of the
pons to form basilar art, which gives off the
cerebellar arteries.
• The basilar artery divides into the posterior
cerebral arteries;
: which supply the occipital lobe and medial side of the
temporal lobe
– The posterior communicating arteries form the
anastomoses between the internal carotids and
posterior cerebral arteries that completing circle of
willis.

5. Circle of Willis
• is a circle of arteries that supply blood to the
brain and surrounding structures.
• is composed of the following arteries:
- Anterior cerebral artery (left and right)
- Anterior communicating artery
- Internal carotid artery (left and right)
- Posterior cerebral artery (left and right)
- Posterior communicating artery (left and right)
- The basilar artery and middle cerebral arteries

9. • The arrangement of the brain's arteries into the Circle of Willis
creates redundancies or collaterals in the cerebral circulation.
• If one part of the circle becomes blocked or narrowed
(stenosed), blood flow from the other blood vessels can often
preserve the cerebral perfusion to avoid the symptoms of
ischemia.

10. Venous drainage of the brain…
• Blood is drained into superficial and deep cerebral veins and
veins of the posterior fossa.
• The superficial veins drain the surface of the brain cortex and
lie within the cortical sulci.
• The deep cerebral veins drain the white matter, basal ganglia,
diencephalon, cerebellum and brainstem.
• The deep vein join to form the great cerebral vein.

11. • Emissary veins connect the veins near the surface of the skull
to the diploic veins and venous sinuses.
• All blood is drained into the meningeal sinuses, which mainly
drain into the internal jugular vein.
• The veins and sinuses of the brain lack valves; pressure of
drainage vessels in the neck is directly transmitted to
intracranial venous structures.

13. CEREBROSPINAL FLUID
CSF

14. Formation of CSF…
• CSF is present in the:
- ventricles of the brain
- cisterns around the brain
- subarachnoid space around the brain and the spinal cord
• Total volume of CSF is ~ 150mls; specific gravity is 1.002 to 1.009
• The daily production is 500 to 600mls/day
: turns over 3 – 4 times/day
• Formed by:
- modified ependymal cells in choroid plexus (>67%)
- directly from the ependyma of the walls of the ventricle
(<33%)

15. • the composition depends on filtration and diffusion from the
cerebral vessels, plus facilitated diffusion and active transport,
predominantly from the choroid plexus
• formation is constant independent of ventricular pressure
• Normal ICP is 5 to 15 mmHg
• when pressure falls below ~ 7 cmH2O absorption ceases

17. Cerebrospinal Fluid
Figure 9-5: ANATOMY SUMMARY: Cerebrospinal Fluid

18. Functions of CSF…
1) Protective role due to water bath effect
- Major fx in protecting brain from injury; act
as a cushion with changes in position or
movement
- give 1400g brain an effective net weight
only 50g
- Allow brain to maintain its density without
being impaired its own weight

19. 2) Regulation in intracranial pressure
- Protective role in buffering any rise in ICP by
CSF translocation to the extracranial
subarachnoid space
3) Return of the interstitial protein to the circulation
- Brain does not have lymph vessel
- Interstitial protein can return to the circulation by absorption
with CSF across the arachnoid villi

20. 4)Role of CSF in control of respiration
- Central chemoreseptor are sensitive to changes in H+
concentration
- H+ act as indirect measure for PaCO2 and stimulate
chemoreseptor
- Changes in PaCO2, but not arterial PH, reflecting the ability of
CO2 to cross blood brain barrier easily
- As a result acute respiratory acidosis or alkalosis produces
corresponding changes in CSF

22. Cerebral perfusion pressure
CPP

23. CPP…
• The pressure driving the flow of blood through the brain
• Obtained from the difference between the mean arterial
pressure (MAP) and the intracranial pressure (ICP)
• CPP = MAP – ICP ( or CVP ; which one is higher )
• Manipulation of CBF  affect ICP ; hence CPP

24. • Under normal circumstances MAP of 90 mmHg and ICP of ~
10 mmHg will give CCP of 80 mmHg
• CPP less than 70 mm Hg lead to rapid decrease in
jugularvenous bulb saturations representing an increased
oxygen extraction by brain tissue
• CPP of 30 – 40 mmHg is the threshold for critical ischaemia
• CPP:
– < 50mmHg  slowing of the EEG
– 25 – 40 mmHg  isoelectric EEG
– < 25 mmHg  irreversible brain damage

25. INTRACRANIAL PRESSURE
the normal contents of the cranium are;
• 1. brain - neural tissue & interstitial fluid ~ 1400g
• 2. blood ~ 75 ml
• 3. CSF ~ 75 ml (+75 ml spinal cord)
• 4. ICP ~ 7-18 cmH2O ( 5 – 15 mm Hg )
because each of these three components is
relatively incompressible, the combined volume
at any one time must be constant ® the Monro-
Kellie doctrine

26. CEREBRAL BLOOD FLOW
CBF

27. Cerebral blood flow (CBF)
• CBF averages 50ml/100g/minute of brain tissue.
• For an adult,this is equivalent to 750ml/minute,or
about 15% of the resting cardiac out put , delivered to
an organ that represents only about 2% of the body’s
mass.
• the gray matter of the brain has a higher cerebral
blood flow (80ml/100g/minute) than the white matter
(20ml/100g/minute)
• The amount of CBF is critical:
• If falls to 20ml/100g/min EEG slow; at 15ml/100g/min
EEG is flat,and at 10ml/100g/min irreversible cerebral
demage occurs.

28. Regulation of cerebral blood flow
• Anesthetic drugs cause dose-related and reversible in
many aspects of cerebral physiology; including CBF ,
CMR , electrophysiologic function(EEG)
• Adult human brain weighs approximately 1350g and is
about 2% of total body weight.
• However , it receives 12% to 15% of cardiac output
• This high flow rate is a reflection of the brain’s high
metabolic rate.
• At rest , brain consumes O2 at an average rate of
3.5mlof O2 per 100g of brain tissue per minute.
• Whole brain O2 consumption(50ml/min) represents
about 20% of total-body O2 utilization.

29. Normal values for CBF,CMR and other
physiologic variables
• Normal cerebral physiologic values
CBF
-GLOBAL 45-55ml/100g/min
-CORTICAL(GRAY MATTER) 75-80ml/100g/min
-SUBCORTICAL(WHITE ~20ml/100g/min
MATTER)
CMRO2 3.0~3.5ml/100g/min
CVR 1.5~2.1 mmHg/100g/min
CEREBRAL VENOUS PO2 32-44 mmHg
CEREBRAL VENOUS SO2 55%- 70%
ICP (SUPINE) 8-12mmHg

30. • Approximately 60% of the brain’s energy
consumption is used to support
electrophysiologic function.
• The remainder of the energy consumed by the
brain is involved in cellular homeostatic activities.
• There are elaborate mechanisms for regulation of
CBF.
• These mechanisms , which include chemical ,
myogenic and neurogenic factors

31. Factors influencing cerebral blood flow
factor factor
CHEMICAL MYOGENIC
CMR Autoregulation / MAP
anesthetics
temperature BLOOD VISCOSITY
PaCO2
PaO2 NEUROGENIC
VASODILATOR DRUGS Extracranial sympathetic and
parasympathetic pathways
anesthetics Intra-axial pathway
vasodilators
vasopressors

32. Chemical regulation of Cerebral Blood
Flow
• Several factors , including changes in CMR ,
PaCO2 , and PaO2 , cause alterations in the
cerebral biochemical environment that result
in adjustment in CBF.

33. Cerebral Metabolic Rate(CMR)
• Increase neuronal activity results in increased local brain
metabolism , and this increase in CMR is associated with a well-
matched , proportional change in CBF and is referred to as –
flow-metabolism coupling.
• Glutamate , released with increased neuronal activity , results in the
synthesis and release of nitric oxide (NO) , A potent cerebral
vasodilator that plays an important role in coupling of flow and
metabolism.
• Flow-metabolism coupling within the brain is a complex physiologic
progress that is regulated , not by a single mechanism , but by a
combination of metabolic , glial , neural , and vascular factors.

34. • FUNCTIONAL STATE.
CMR is influenced by • CMR decreases during sleep and increases
several phenomena in during sensory stimulation , aruosal of any
the neurosurgical cause.
environment • During epileptic activity , CMR increase
including… extremely,whereas regionally after brain
injury and globally with coma,CMR may be
substantially reduced.
• ANESTHETIC DRUGS.
1) The functional
• In general,anesthetic drugs suppress CMR ,
state with ketamine and N2O being notable
exception.
2) Anesthetic drugs • TEMPERATURE.
• The effects of hypothermia on the brain
3) Temperature have been reveiwed in detail.
• CMR decreases by 6%-7% per degree
Celsius of temperature reduction.

35. PaCO2
• CBF varies directly with Paco2. the effect is greatest within the
range of physiologic Paco2 variation
• CBF changes 1 to 2 ml/100g/min for each 1-mmHg change in Paco2
around normal Paco2 values.
• The changes in CBF caused by Paco2 are dependent on pH
alterations in the extracellular fluid of the brain.
• NO(nitric oxide),in particular NO of neuronal origin, is an important
although not exclusive mediator of C02-induced vasodilation.
• The vasodilatory response to hypercapnia is also mediated in part
by prostaglandins.
• Note that in contrast with respiratory acidosis, systemic metabolic
acidosis has little immediate effect on CBF because the BBB
excludes hydrogen ion (H+) from the perivascular space.

36. PaO2
• Changes in Pao2 from 60 to greater than
300mmHg have little influence on CBF. Below a
Pao2 of 60 mmHg, CBF increases rapidly.
• The mechanisms mediating cerebral vasodilation
during hypoxia are not fully unserstood but may
include neurogenic effects initiated by peripheral
and neuraxial chemoreceptors,aw well as local
humoral influences.

37. • Paco2 and Pao2 influence cerebral blood flow ,
whereas sympathetic and parasympathetic nerves play
little or no role in the regulation of CBF
• Changes in the Paco2 between about 20 and 80 mmHg
produce corresponding changes in CBF
• CO2 increases CBF by combining with water in body
fluids to form carbonic acid , with subsequent
dissociation to form hydrogen ions.
• Hydrogen ions produce vasodilatation of cerebral
vessels that is proportional to the increase in hydrogen
ion concentration

38. • Any other acid that increases hydrogen ion
concentration , such as lactic acid , also increases CBF
• Increased CBF in response to increases in Paco2 serves
to carry away excess hydrogen ions that would
otherwise greatly depress neuronal activity
• Unlike the continuous response of CBF to changes in
Paco2,the response to Pao2 is a threshold
phenomenon
• If the Paco2 is maintained , CBF begins to increase
when the Pao2 decreases below 50 mmHg or the
cerebral venous Po2 decreases from its normal value of
35 mmHg to about 30 mmHg.

40. Myogenic
regulation(AUTOREGULATION) of CBF
• AOTUREGULATION refers to the capacity of the cerebral circulation to adjust its
resistance to maintain CBF constant over a wide range of mean arterial pressure.
• The limits of autoregulation occurring at MAP values of ~70 and 150mmHg(60 and
140mmHg Stoelting)
• The lower limit of autoregulation(LLA) has been widely quoted as an MAP of
50mmHg.
• Above and below the autoregulation plateau, CBF is pressure dependent(pressure
passive) and varies linearly with CPP.
• Autoregulation is influenced by various pathologic processes, as well as the time
course over which the changes in CCP occur.
• Even within the range over which autoregulaiton normally occurs, a rapid change
in arterial pressure will result in a transient(3-4 minutes)alteration in CBF.
• According to the myogenic hypothesis, changes in CPP lead to direct changes in
the tone of vascular smooth muscle:this progress appears to be passive.

41. • CBF is closely autoregulated btw a mean
arterial pressure of abt 60 and 140mmHg
• As a result, changes in systemic blood
pressure within this range will not significantly
alter CBF
• Chronic systemic hypertension shifts the
autoregulation curve to the right such that
decreases in CBF occur at a mean arterial
pressure of >60 mmHg

43. • Autoregulation of CBF is attenuated or abolished by
hypercapnia, arterial hypoxemia, and volatile anesthetics.
• Autoregulaition is often abolished in the area surrounding
an acute cerebral infarction.
• Increases in mean arterial pressure above the limits of
autoregulation can cause leakage of intravascular fluid
through capillary membranes, resulting in cerebral edema.
• Because the brain is enclosed in a solid vault, the
accumulation of edema fluid increases intracranial pressure
and compress blood vessels, decreasing cerebral blood flow
and leading to destruction of brain tissue.

44. Neurogenic regulation of CBF
• The cerebral vasculature is extensively innervated
• The density of innervation declines with vessel size, and the greatest
neurogenic influence appears to be exerted on larger cerebral arteries.
• Evidence of the functional significance of neurogenic influences has been
derived from studies of CBF autoregulation and ischemic injury
• Hemorrhagic shock, a state of high sympathetic tone, results in a lower
CBF at a given MAP than occurs when hypotension is produced with
sympatholytic drugs, presumably because during shock, a sympathetically
mediated vasoconstrictive effect shifts the power end of the
“autoregulation” plateau to the right .
• It is not clear what the relative contributions of humoral and neural
mechanism are to this phenomenon;however,there is certainly a
neurogenic component in somespecies because sympathetic denervation
increases CBF during hemorrhagic shock.

45. Effect of blood viscosity on CBF
• Blood viscosity can influence CBF.Hematocrit is
the single most important determinant of blood
viscosity
• In healthy subjects,variation of the hematocrit
within the normal range(33%-45%) probably
results in only modest alterations in CBF
• Beyond this range,changes are more substantial
• In anemia, cerebral vascular resistance is reduced
and CBF increases

46. Effect of anesthetics on CBF
Intravenous anesthetic drugs Volatile anesthetics
• Barbiturates • Halothane
• Propofol
• Etomidate
• Narcotics
• Benzodiazepines
• Ketamine
• Lidocaine

47. Effect of anesthetics on CBF
• Intravaneous anesthetic drugs
• The vast majority of intravenous anesthetics
cause a reduction in both CMR and CBF.
• Ketamine, which causes an increase in CMR
and CBF, is the exception.

48. barbiturates
• A dose-dependent reduction in CBF and CMR
occurs with barbiturates.
• With the onset of anesthesia, CBF and CMR02
are reduces by about 30%
• When large doses of thiopental cause
complete EEG suppression, CBF and CMR are
reduced by about 50%
• Further increases in the dose of barbiturate
have no additional effect on CMR.

49. Barbiturate coma
• is a temporary coma (a deep state of
unconciousness) brought on by a controlled
dose of a barbiturate drug, usually
pentobarbital or thiopental.
• Barbiturate comas are used to protect the
brain during major neurosurgery, and as a last
line of treatment in certain cases of status
epilepticus that have not responded to other
treatments.

50. Barbiturate coma
• Barbiturates reduce the metabolic rate of brain
tissue, as well as the CBF. With these reductions,
the blood vessels in the brain narrow, decreasing
the amount of volume occupied by the brain, and
hence the intracranial pressure.
• The hope is that, with the swelling relieved, the
pressure decreases and some or all brain damage
may be averted. Several studies have supported
this theory by showing reduced mortality when
treating refractory intracranial hypertension with
a barbiturate coma.

51. Barbiturate coma
• Some studies have shown that barbiturate-
induced coma can reduce intracranial
hypertension but does not necessarily prevent
brain damage.
• Furthermore, the reduction in intracranial
hypertension may not be sustained.

52. Barbiturate coma
• Some randomized trials have failed to
demonstrate any survival or morbidity benefit
of induced coma in diverse conditions such as
neurosurgical operations, head trauma,
intracranial anurysm rupture,intracranial
hemorrhage, ischemic stroke, and status
epilepticus.
• If the patient survives, cognitive impairment
may also follow recovery from the coma.

53. propofol
• The effects of propofol on CBF and CMR appear to be quite
similar to those of barbiturates.
• Substantial reductions in both CBF and CMR after the
administration of propofol
• Surgical levels of propofol reduced regional CBF by 53% to
79% in comparison with the awake state.
• When compared with isoflurane-fentanyl or sevoflurane-
fentanyl anesthesia, a combination of propofol-fentanyl
decreased subdural pressure in patients with intracranial
tumors and decreased the arteriovenous oxygen content
difference
• Propofol effects reduces in CMR and secondarily decreases
CBF,CBV and ICP

54. narcotics
• Narcotics have relatively little effect on CNF
and CMR in the normal , unstimulated
nervous system
• When changes do occur, the general pattern
in one of modest reductions in both CBF and
CMR

55. benzodiazepines
• Cause parallel reductions in CBF and CMR
• CBF and CMRO2 decreased by25% when 15mg of diazepam
was given to head-injured patients
• The effects of midazolam on CBF(but not CMR) have also
studied in humans.
• Foster and associates observed a 30%-34% reduction in CBF
after the administration of 0.15mg/kg of midazolam to
awake healthy human .
• Veselis and coworkers ,using PET observed a global 12%
reduction in CBF after a similar dose and noted that the
decreases occurred preferentially in the brain regions
associated with arousal, attention, and memory

56. ketamine
• Among the intravenous anesthetics, ketamine is unique in its ability
to cause increases in both CBF and CMR
• PET studies in humans have demonstrated that subanesthetic doses
of ketamine(0.2 to 0.3mg/kg)can increase global CMR by about 25%
• Commercially available formulations of ketamine contain both the
(s)-and (R) –ketamine enantiomers.
• The (s)-ketamine enantiomer increases CMR substantially,whereas
the (R) enantiomer tends to decrease CMR,particularly in the
temporomedial cortex and in the cerebellum
• These changes in CMR are accompanied by corresponding changes
in CBF
• The observed effects of ketamine on cerebral hemodynamics
indicate that ketamine increase CMR and secondarily increases CBF,
CO2 responsiveness is preserved

57. ketamine
• The anticipated ICP correlate of the increasein CBF has
been confirmed to occur in humans.
• However , anesthetiv drugs(diazepam, midazolam,
isoflurane/N20, propofol)have been shown to blunt or
eliminate the increases in ICP or CBF associated with
ketamine
• Accordingly, although ketamine is probably best
avoided as the sole anesthetic agent in patients with
impaired intracranial compliance, it may be reasonable
to use it cautiously in patients who are simultaneously
receiving the other drugs mentioned earlier

58. Volatile anesthetics
• The pattern of volatile anesthetic effects on cerebral
physiology is a striking depature from that observed with
the intravenous aneathetics, which generally cause parallel
reductions in CMR and CBF.
• All volatile anesthetics, suppress cerebral metabolism in a
dose-related manner
• Volatile anesthetics also possess intrinsic cerebral
vasodilatory activity as a result of direct effects on vascular
smooth muscle
• The net effect of volatile anesthetics on CBF is therefore a
balance between a reduction in CBF caused by CMR
suppression and augmentation of CBF caused by the direct
cerebral vasodilation .

59. Volatile anesthetics
• When administered at a dose of 0.5 MAC,CMR suppression-induced
reduction in CBF predominates, and net CBF decreases in
comparison to the awake state.
• At 1.0 MAC, CBF remains unchanged; at this dose, CMR suppression
and vasodilatory effects are in balance.
• Beyond 1.0 MAC, the vasodilatory activity predominates, and CBF
increases significantly even though CMR is substantially reduced.
• The important clinical consequences of administration of volatile
anesthetics are derived from the increases in CBF and CBV– and
consequently ICP – that can occur.
• Of the commonly used volatile anesthetics, the order of
vasodilating potency is approximately halothane >> enflurane >
desflurane ~ isoflurane > sevoflurane.

60. Thank you
References
Miller’s Anesthesia
Pharmacology&physiology(stoelting)