CSF Physiology and Cerebral Blood Flow Keith R. Lodhia, MD,MS Department of Neurosurgery University of Michigan 12/20/03.

CSF Physiology and CSF Physiology and Cerebral Blood FlowCerebral Blood Flow

Keith R. Lodhia, MD,MSDepartment of Neurosurgery

University of Michigan12/20/03

CSF FunctionsCSF Functions

provide mechanical protection provide mechanical protection maintain a stable extracellular maintain a stable extracellular

environment for the brain environment for the brain Remove some waste productsRemove some waste products nutritionnutrition Convey messages? (hormones/releasing Convey messages? (hormones/releasing

factors/neurotransmitters)factors/neurotransmitters)

Brain Fluid “Balance”

CSF ProductionCSF Production

70 % CSF produced in 70 % CSF produced in choroid plexuses of lateral, choroid plexuses of lateral, third and fourth ventricles third and fourth ventricles

produced at rate of 500 produced at rate of 500 cc/day or approximately cc/day or approximately 20cc/hour (0.3-0.5 20cc/hour (0.3-0.5 cc/kg/hr)cc/kg/hr)

eliminated by being eliminated by being absorbed into the absorbed into the arachnoid villi --> dural arachnoid villi --> dural sinus --> jugular system sinus --> jugular system

The secretion of fluid by the The secretion of fluid by the choroid plexus depends on choroid plexus depends on the active Na+-transport the active Na+-transport across the cells into the across the cells into the CSF. The electrical gradient CSF. The electrical gradient pulls along Cl-, and both pulls along Cl-, and both ions drag water by osmosis. ions drag water by osmosis. The CSF has lower [K+], The CSF has lower [K+], [glucose], and much lower [glucose], and much lower [protein] than blood plasma, [protein] than blood plasma, and higher concentrations of and higher concentrations of Na+ and Cl-. The production Na+ and Cl-. The production of CSF in the choroid of CSF in the choroid plexuses is an active plexuses is an active secretory process, and not secretory process, and not directly dependent on the directly dependent on the arterial blood pressure. arterial blood pressure.

CSF ProductionCSF Production

Other sources of CSF production from Other sources of CSF production from capillary ultrafiltrate (Virchow-Robin capillary ultrafiltrate (Virchow-Robin spaces)spaces)

Additionally some produced from Additionally some produced from metabolic Hmetabolic H22O productionO production

CSF ProductionCSF Production

Virchow-Virchow-Robin Robin spacesspaces

CSF PRODUCTION- Choroid CSF PRODUCTION- Choroid PlexusPlexus

CSF is produced by CSF is produced by choroid plexus and choroid plexus and secreted at ciliated secreted at ciliated cuboidal epithelial cuboidal epithelial cell surfaces of the cell surfaces of the microvilli into the microvilli into the ventriclesventricles

CSF PRODUCTION- Choroid CSF PRODUCTION- Choroid PlexusPlexus

Ependymal Cell Membrane Ependymal Cell Membrane TransportTransport

CSF ProductionCSF Production

CSF secretion CSF secretion involves the involves the transport of transport of ions ( Na+, Cl¯ ions ( Na+, Cl¯ and HCO3¯) and HCO3¯) across the across the epithelium epithelium from blood to from blood to CSF CSF Basolateral Apical

H20, Na+, HCO3¯, Cl¯

Secretion can occur because of the polarized distribution of specific ion transporters in the apical or basolateral membrane of the epithelial cells.

CSF ProductionCSF Production

5-HT5-HT2C2C receptors receptors– from 5HT subfamily. – from 5HT subfamily. {e.g 1) SSRI’s block 5-HT{e.g 1) SSRI’s block 5-HT1A1A receptor receptor presynaptic uptake of 5HT 2) antimigraine presynaptic uptake of 5HT 2) antimigraine “triptans” stimulate vasoconstriction- “triptans” stimulate vasoconstriction- agonists mediating 5HTagonists mediating 5HT1B1B//1D 1D receptors 3) receptors 3) ondansetron/granisetron are 5-HTondansetron/granisetron are 5-HT33 receptor receptor antagonists - antinaseau effects}antagonists - antinaseau effects}

5-HT5-HT2C2C receptors found in high receptors found in high concentration in choroid plexusconcentration in choroid plexus

CSF ProductionCSF Production

ANP receptors found in choroid ANP receptors found in choroid plexusplexus

ANP decreases CSF production ANP decreases CSF production Choroid plexus epithelial cells Choroid plexus epithelial cells

express receptors for atrial express receptors for atrial natriuretic peptide that when natriuretic peptide that when stimulated increase cGMP levels stimulated increase cGMP levels and inhibit cerebral spinal fluid and inhibit cerebral spinal fluid production production

Aquaporin-AQP1 channels are Aquaporin-AQP1 channels are thought to be involved in the thought to be involved in the production of cerebral spinal fluid production of cerebral spinal fluid

CSF ConstituencyCSF Constituency

CSF volume: 25 cc CSF volume: 25 cc ventricular, 25cc ventricular, 25cc intracranial intracranial subarachnoid subarachnoid space, and 100cc space, and 100cc in spinal in spinal subarachnoid subarachnoid spacesspaces

ββ22 transferrin transferrin

CSF Constituency- CSF Constituency- ββ22 transferrin transferrin

PROTEIN ELECTROPHORESIS-PROTEIN ELECTROPHORESIS-on cellulose/PAGE/filter etcon cellulose/PAGE/filter etc

Transferrin is an iron binding Transferrin is an iron binding protein used to shuttle iron protein used to shuttle iron stores to cells- marker of stores to cells- marker of severe malnutrition . severe malnutrition . Elevations in: Elevations in: hypothyroidism, biliary hypothyroidism, biliary cirrhosis, nephrosis, chronic cirrhosis, nephrosis, chronic iron deficient anemia, and iron deficient anemia, and some cases of diabetes some cases of diabetes

CSF shows increased CSF shows increased ββ22 peak peak c/w mucous. Therefore c/w mucous. Therefore useful in evaluating potential useful in evaluating potential CSF rhinorrheaCSF rhinorrhea

CSF CirculationCSF Circulation lateral ventricles--> lateral ventricles-->

foramen of Monro foramen of Monro third ventricle --> third ventricle --> aqueduct of Sylvius --aqueduct of Sylvius --> fourth ventricle --> > fourth ventricle --> foramina of Magendie foramina of Magendie and Luschka --> and Luschka --> subarachnoid space subarachnoid space over brain and spinal over brain and spinal cord --> reabsorption cord --> reabsorption into venous sinus into venous sinus blood via arachnoid blood via arachnoid granulationsgranulations

CSF CirculationCSF Circulation

Lundberg WavesLundberg Waves Lundberg has described 3 wave patterns ICP waves (A,

B, and C waves). A waves are pathological. There is a rapid rise in ICP up to 50-100 mm Hg followed by a variable period during which the ICP remains elevated followed by a rapid fall to the baseline and when they persist for longer periods, they are called 'plateau' waves which are pathological. 'Truncated' or atypical ones, that do not exceed an elevation of 50 mm Hg, are early indicators of neurological deterioration. B & C waves are related to respiration and 'Traube-Hering-Mayer' waves (rhythmical variations in blood pressure) respectively and are part of normal physiology with little clinical significance. 

LundbergA- waves

A- waves/Plateau WavesA- waves/Plateau Waves Steep rises and abrupt falls in ICP, peaking at 50-100 Steep rises and abrupt falls in ICP, peaking at 50-100

mm Hg, that last 5- 20 minutes (also known as mm Hg, that last 5- 20 minutes (also known as plateau waves). plateau waves).

May signify intracranial vasomotor decompensation. May signify intracranial vasomotor decompensation. May or may not be associated with clinical May or may not be associated with clinical deterioration.deterioration.

Pathogenesis related to dilation of resistance Pathogenesis related to dilation of resistance vessels, increased intracranial blood volume, vessels, increased intracranial blood volume, decreased flow, and increased pressure. decreased flow, and increased pressure.

““Loss of Autoregulation”Loss of Autoregulation”

CSF AbsorptionCSF Absorption

CSF is reabsorbed into CSF is reabsorbed into the blood of the the blood of the venous sinuses via the venous sinuses via the arachnoidal villi. The arachnoidal villi. The absorption here is absorption here is directly related to the directly related to the CSF pressure in the CSF pressure in the cranial cavity. cranial cavity.

Lymphatics/cribiform Lymphatics/cribiform plateplate

Transependymal flowTransependymal flow

Route and Absorption of Route and Absorption of CSFCSF

Arachnoid villi are Arachnoid villi are microscopic one-way valves microscopic one-way valves (modified pia and arachnoid) (modified pia and arachnoid) that penetrate the meningeal that penetrate the meningeal dural layer that line the dural layer that line the sinuses; hence, arachnoid sinuses; hence, arachnoid villi reside within the sinuses villi reside within the sinuses (especially the superior (especially the superior sagittal sinus).sagittal sinus).

Clumps of arachnoid villi = Clumps of arachnoid villi = arachnoid granulationsarachnoid granulations = = macroscopic.macroscopic.

Arachnoid Villus

Route and Absorption of Route and Absorption of CSFCSF Hydrostatic pressure in subarachnoid Hydrostatic pressure in subarachnoid

space > pressure in dural sinusesspace > pressure in dural sinuses Typical hydrostatic values of CSF are 150 Typical hydrostatic values of CSF are 150

mm Hmm H22O (11 mm Hg) in subarachnoid O (11 mm Hg) in subarachnoid space vs. about 70 mm Hspace vs. about 70 mm H22O (5 mm Hg) in O (5 mm Hg) in dural sinuses.dural sinuses.

Arach. villi are Arach. villi are one-way valvesone-way valves that that open when the hydrostatic pressure of open when the hydrostatic pressure of CSF in the subarachnoid space is about CSF in the subarachnoid space is about 1.5 mm Hg greater than venous 1.5 mm Hg greater than venous hydrostatic pressure in the dural hydrostatic pressure in the dural sinuses (i.e., passive process).sinuses (i.e., passive process).

Drugs affecting Rate ofDrugs affecting Rate ofCSF ProductionCSF Production

DrugsDrugs Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors

(acetozolamide/Diamox)(acetozolamide/Diamox) Cardiac glycosides (digoxin) inhibit Cardiac glycosides (digoxin) inhibit

ATPase pump, thereby reducing CSF ATPase pump, thereby reducing CSF formation in a dose-dependent manner.formation in a dose-dependent manner.

Steroids- Effects on CSF formation are Steroids- Effects on CSF formation are inconsistent.inconsistent.

Future- AqP inhibitors?, 5-HTFuture- AqP inhibitors?, 5-HT2C2C receptor receptor inh ?inh ?

CSF Pharmacology cont.CSF Pharmacology cont.

Carbonic AnhydraseCarbonic Anhydrase CO2 + H2O CO2 + H2O

<=H2Co3=> HCO3- + <=H2Co3=> HCO3- + H+H+

Inhibition of CAII Inhibition of CAII decreases production decreases production of CSF by 60 % by of CSF by 60 % by decreasing decreasing bicarbonate formation bicarbonate formation in choroid plexusin choroid plexus

Acute Mountain Acute Mountain Sickness- an aside. Sickness- an aside.

CO2 + H2O <=> HCO3- + H+

VENTRICLEVENTRICLE

Acute Mountain Sickness-Acute Mountain Sickness-AMSAMS

AMS symptoms (HA fatigue AMS symptoms (HA fatigue somnolence etc) represent somnolence etc) represent the effect of early cerebral the effect of early cerebral edema with increased edema with increased intracranial pressure intracranial pressure

a loss of cerebral a loss of cerebral autoregulation mechanisms autoregulation mechanisms leading to vasogenic edema leading to vasogenic edema (also migrainous-like), or an (also migrainous-like), or an osmotic swelling of the brain osmotic swelling of the brain cells (cytotoxic edema). cells (cytotoxic edema).

Hypoventilation appears to Hypoventilation appears to contribute to development of contribute to development of AMS. A brisk increase in AMS. A brisk increase in ventilation on ascent to ventilation on ascent to altitude is associated with a altitude is associated with a lower incidence of AMS lower incidence of AMS

Acute Mountain Sickness-Acute Mountain Sickness-AMSAMS

Prophylaxis: slow ascent, Diamox, Prophylaxis: slow ascent, Diamox, Rx: ASA or tylenol for mild HARx: ASA or tylenol for mild HA Acute therapy for High Altitude Acute therapy for High Altitude

Cerebral Edema (severe form of Cerebral Edema (severe form of AMS): decadron, but descent to a AMS): decadron, but descent to a lower altitude is still the most lower altitude is still the most reliable treatment reliable treatment

CSF PathologyCSF Pathology In cases of subarachnoid hemorrhage or traumatic In cases of subarachnoid hemorrhage or traumatic

spinal fluid taps, approximately 1 WBC is added to spinal fluid taps, approximately 1 WBC is added to every 700 RBCs (literature range, 1 WBC/500-1,000 every 700 RBCs (literature range, 1 WBC/500-1,000 RBCs). This disagreement in values makes formulas RBCs). This disagreement in values makes formulas (Fisher ratio etc) unreliable that attempt to (Fisher ratio etc) unreliable that attempt to differentiate traumatic tap artifact from true WBC differentiate traumatic tap artifact from true WBC increase. Also, the presence of subarachnoid blood increase. Also, the presence of subarachnoid blood itself may sometimes cause meningeal irritation, itself may sometimes cause meningeal irritation, producing a mild to moderate increase in PMNs after producing a mild to moderate increase in PMNs after several hours that occasionally may be greater than several hours that occasionally may be greater than 500 WBCs/ mm3 . 500 WBCs/ mm3 .

Xanthochromia begins in > 4 hours (literature range, 2-Xanthochromia begins in > 4 hours (literature range, 2-48 hours) due to hemoglobin pigment from lysed RBCs. 48 hours) due to hemoglobin pigment from lysed RBCs.

CSF PathologyCSF PathologyPatterns of Cerebrospinal Fluid Abnormality: Cell Type and Glucose Level

POLYMORPHONUCLEAR: LOW GLUCOSE Acute bacterial meningitis

POLYMORPHONUCLEAR: LOW OR NORMAL GLUCOSE Some cases of early phase acute bacterial meningitis

Primary amoebic (Naegleria species) meningoencephalitis

Early phase Leptospira meningitis

POLYMORPHONUCLEAR: NORMAL GLUCOSE Brain abscess

Early phase coxsackievirus and echovirus meningitis

CNS syphilis (some patients)

Acute bacterial meningitis with IV glucose therapy

Listeria (about 20% of cases)

LYMPHOCYTIC: LOW GLUCOSE Tuberculosis meningitis

Cryptococcal (Torula) meningitis

Mumps meningoencephalitis (some cases)

Meningeal carcinomatosis (some cases)

Meningeal sarcoidosis (some cases)

Listeria (about 15% of cases)

LYMPHOCYTIC: NORMAL GLUCOSE Viral meningitis

Viral encephalitis

Postinfectious encephalitis

Lead encephalopathy

CNS syphilis (majority of patients)

Brain tumor (occasionally)

Leptospira meningitis (after the early phase)

Listeria (about 15% of cases)

Cerebral Blood Flow (CBF)Cerebral Blood Flow (CBF)

CBF = CBV/tCBF = CBV/t 750 mL/minute, which is 15% of the 750 mL/minute, which is 15% of the

cardiac output cardiac output The normal cerebral blood flow is 45-The normal cerebral blood flow is 45-

50ml/100g/min, ranging from 50ml/100g/min, ranging from 20ml 100g-1 min-1 in white matter to 20ml 100g-1 min-1 in white matter to 70ml 100g-1 min-1 in grey matter. 70ml 100g-1 min-1 in grey matter. Highest in neurohypophysisHighest in neurohypophysis

CBFCBF

When CBF falls to less than 10-When CBF falls to less than 10-23ml/100g/min, physiological 23ml/100g/min, physiological electrical function of the cell begins electrical function of the cell begins to fail- “ischemic penumbra”. to fail- “ischemic penumbra”.

Below 8 ml/100g/min irreversible cell Below 8 ml/100g/min irreversible cell death- ionic membrane transport death- ionic membrane transport failurefailure

Cerebral Perfusion Pressure Cerebral Perfusion Pressure (CPP)(CPP)

Cerebral Perfusion Pressure (CPP)Cerebral Perfusion Pressure (CPP)

MAP-ICP=CPPMAP-ICP=CPP

normal CPP is between 50-150 mmHgnormal CPP is between 50-150 mmHg <50 mmHg --> ischemia <50 mmHg --> ischemia >150 mmHg --> hyperemia >150 mmHg --> hyperemia

AutoregulationAutoregulation CBF is maintained at a constant level in normal CBF is maintained at a constant level in normal

brain in the face of the usual fluctuations in brain in the face of the usual fluctuations in blood pressure by the process of autoregulation. blood pressure by the process of autoregulation. It is a poorly understood local vascular It is a poorly understood local vascular mechanism. Normally autoregulation maintains mechanism. Normally autoregulation maintains a constant blood flow between CPP 50 mmHg a constant blood flow between CPP 50 mmHg and 150 mmHg. and 150 mmHg.

Poiseuille’s law- flow through a rigid vessel: Poiseuille’s law- flow through a rigid vessel:

Q = Q = ΔΔPPππrr44/8L/8Lηη

AutoregulationAutoregulation

Dysregulation can occur in pathologic statesDysregulation can occur in pathologic states In traumatised or ischaemic brain, or In traumatised or ischaemic brain, or

following vasodilator agents (volatile agents following vasodilator agents (volatile agents and sodium nitroprusside) CBF may become and sodium nitroprusside) CBF may become blood pressure dependent. Thus as arterial blood pressure dependent. Thus as arterial pressure rises so CBF will rise causing an pressure rises so CBF will rise causing an increase in cerebral volume. Similarly as increase in cerebral volume. Similarly as pressure falls so CBF will also fall, reducing pressure falls so CBF will also fall, reducing ICP, but also inducing an uncontrolled ICP, but also inducing an uncontrolled reduction in CBF. reduction in CBF.

pressure/myogenic autoregulationpressure/myogenic autoregulation arterioles dilate or constrict in response to changes arterioles dilate or constrict in response to changes

in BP and ICP in order to maintain a constant CBF in BP and ICP in order to maintain a constant CBF ““myogenic theory”- vascular smooth muscle within myogenic theory”- vascular smooth muscle within

cerebral arterioles intrinsically contract to stretch cerebral arterioles intrinsically contract to stretch thereby regulating pressurethereby regulating pressure

NO- limited role overall, but if completely abolish NO NO- limited role overall, but if completely abolish NO production then loss of autoregulation; with CBF production then loss of autoregulation; with CBF being completely BP-dependentbeing completely BP-dependent

AutoregulationAutoregulation

Metabolic AutoregulationMetabolic Autoregulation

arterioles dilate in response to potent chemicals that are by-products of metabolism such as lactic acid, carbon dioxide and pyruvic acid

CO2 is a potent vasodilator increased CO2/decreased BP --> vasodilation decreased CO2/increased BP --

>vasoconstriction

Neurogenic AutoregulationNeurogenic Autoregulation

Autonomic- sympathetic adrenergic Autonomic- sympathetic adrenergic receptors seen in cortical layers IV receptors seen in cortical layers IV and V.and V.

ΒΒ11,, β β22, and ą, and ą2 2 (“dilators”), and ą(“dilators”), and ą1 1

(“constrictor”) receptors(“constrictor”) receptors Overall sympathetic system plays Overall sympathetic system plays

minor role unlike in non-cerebral minor role unlike in non-cerebral vascular beds. vascular beds.

Neurogenic Autoregulation- Neurogenic Autoregulation- contcont

5-HT- potent “constrictor,” antagonized by NO5-HT- potent “constrictor,” antagonized by NO Neuropeptide Y- “vasoconstriction”, in assoc Neuropeptide Y- “vasoconstriction”, in assoc

with NO and sympathetic systemwith NO and sympathetic system Vasoactive intestinal polypeptide (VIP) and Vasoactive intestinal polypeptide (VIP) and

peptide histidine isoleucine (PHI)- peptide histidine isoleucine (PHI)- “vasodilators”“vasodilators”

Substance P, neurokinin A, calcitonin gene-Substance P, neurokinin A, calcitonin gene-related peptide histamine Hrelated peptide histamine H22 -”vasodilatory” -”vasodilatory” esp. substance P esp. substance P

CCK, neurotensin, somatostatin, vasopressin, CCK, neurotensin, somatostatin, vasopressin, endorphinendorphin

Neurogenic Autoregulation-Neurogenic Autoregulation-contcont

Autonomic system and Autonomic system and neurochemical control of neurochemical control of CBF in general is a minor CBF in general is a minor controlcontrol

Overall, pressure and Overall, pressure and metabolic autoregulation metabolic autoregulation most importantmost important

Increasing CBF-HyperemiaIncreasing CBF-Hyperemia

Low arterial oxygen Low arterial oxygen tension has tension has profound effects on profound effects on cerebral blood flow. cerebral blood flow. When it falls below When it falls below 50 mmHg (6.7 kPa), 50 mmHg (6.7 kPa), there is a rapid there is a rapid increase in CBF and increase in CBF and arterial blood arterial blood volume volume

CBF and COCBF and CO22

Carbon dioxide Carbon dioxide causes cerebral causes cerebral vasodilation. As the vasodilation. As the arterial tension of arterial tension of CO2 rises, CBV and CO2 rises, CBV and CBF increases and CBF increases and when it is reduced when it is reduced vasoconstriction is vasoconstriction is induced.induced.

““Cerebrovascular Reserve”Cerebrovascular Reserve”

In functionally activated areas, CBF augmentation exceeds the small increases in oxygen utilization and the concentration of deoxyhemoglobin is relatively low. Thus, this excess supply of oxygen in response to a demand stimulus reflects the cerebral perfusion reserve capacity

Cerebrovascular reserve capacity is impaired by risk factors such as hypertension and diabetes, carotid/cerebral vasc. stenosis, and can be an etiologic factor in ischemic stroke

Cerebrovascular ReserveCerebrovascular Reserve

PET, SPECT, Xe-CT, CT-perfusion to assess. Pre/post diamox challenge.

acetazolamide challenge and the CO2-loading (breath-holding) test raise global CBF

(MRI) of T2-weighted or Blood oxygenation level–dependent ( (BOLD)-weighted images correlate well with changes in the total amount of oxygenated hemoglobin

Xenon CT

perfusion CT BOLD-MRI and single-photon emission computed tomography (SPECT) (SPECT)

CBF AND CSF- TYING CBF AND CSF- TYING IT TOGETHERIT TOGETHER

PATHOPHYSIOLOGY CSF/CBFPATHOPHYSIOLOGY CSF/CBF

1. the intracranial compartment is a 1. the intracranial compartment is a rigid container and consists of three rigid container and consists of three componentscomponents

a. brain-80% of total volume a. brain-80% of total volume b. blood-10% of total volume b. blood-10% of total volume c. CSF-10% of total volume c. CSF-10% of total volume

PATHOPHYSIOLOGY CSF/CBFPATHOPHYSIOLOGY CSF/CBF

2. 2. Monro-Kellie Monro-Kellie HypothesisHypothesis

to maintain a normal to maintain a normal ICP, a change in the ICP, a change in the volume of one volume of one compartment must be compartment must be offset by a reciprocal offset by a reciprocal change in the volume of change in the volume of another compartmentanother compartment

pressure is normally pressure is normally well-controlled through well-controlled through alterations in the alterations in the volume of blood and volume of blood and CSFCSF

Brain P/V curve Brain P/V curve

P/V CURVE AND P/V CURVE AND COMPLIANCECOMPLIANCE

Pressure gradients can develop Pressure gradients can develop within the brain substance and the within the brain substance and the compliance or “squishiness” of compliance or “squishiness” of pathological brain (e.g. tumor) can pathological brain (e.g. tumor) can be different from that of normal be different from that of normal brain leading to an altered curve brain leading to an altered curve (shift left). (shift left). The extent of the change in ICP caused by an The extent of the change in ICP caused by an

alteration in the volume of intracranial contents is alteration in the volume of intracranial contents is determined by the compliance or of the brain. In determined by the compliance or of the brain. In other words if compliance is low, the brain is stiffer other words if compliance is low, the brain is stiffer or less "squashable". Therefore, an increase in brain or less "squashable". Therefore, an increase in brain volume will result in a higher rise in intracranial volume will result in a higher rise in intracranial pressure than if the compliance were high. pressure than if the compliance were high.

Blood/Brain-Blood/CSF Blood/Brain-Blood/CSF BarriersBarriers

The blood-brain barrier (BBB) is the The blood-brain barrier (BBB) is the specialized system of capillary endothelial specialized system of capillary endothelial cells that protects the brain from harmful cells that protects the brain from harmful substances in the blood stream, while substances in the blood stream, while supplying the brain with the required supplying the brain with the required nutrients for proper function. nutrients for proper function.

Formed by the nonfenestrated capillaries Formed by the nonfenestrated capillaries and to much lesser degree, the astrocytic and to much lesser degree, the astrocytic foot processes—keeps out most foot processes—keeps out most macromoleculesmacromolecules

Blood/Brain BarrierBlood/Brain Barrier

Blood-Blood-CSF CSF

BarrierBarrier ““Tight” Tight”

junctions at junctions at the the ependymal ependymal levellevel

Fenestrated Fenestrated junctions at junctions at the the choroidal choroidal capillariescapillaries

The choroid plexus is composed of fenestrated capillaries and an epithelial (ependymal) covering, which reverts from "tight" to moderately "open" at the base -–not as strenuous of barrier as blood/brain

Blood/Brain Barrier and Blood/Brain Barrier and Circumventricular organsCircumventricular organs

The circumventricular organs (CVO) are midline The circumventricular organs (CVO) are midline structures bordering the 3rd and 4th ventricles. structures bordering the 3rd and 4th ventricles. These barrier-deficient areas are recognized as These barrier-deficient areas are recognized as important sites for communicating with the CSF important sites for communicating with the CSF and between the brain and peripheral organs via and between the brain and peripheral organs via blood-borne products. CVO's include the pineal blood-borne products. CVO's include the pineal gland, median eminence, neurohypophysis, gland, median eminence, neurohypophysis, subfornical organ, area postrema, subfornical organ, area postrema, subcommissural organ, organum vasculosum of subcommissural organ, organum vasculosum of the lamina terminalis, and the choroid plexus. the lamina terminalis, and the choroid plexus. The intermediate and neural lobes of the pituitary The intermediate and neural lobes of the pituitary are sometimes included are sometimes included

Causes of an increased ICPCauses of an increased ICP

Conditions Increasing Brain VolumeConditions Increasing Brain Volume intracranial mass (tumor, hematoma, intracranial mass (tumor, hematoma,

aneurysm, AVM) aneurysm, AVM) cerebral edema cerebral edema CNS infection (abscess, inflammatory CNS infection (abscess, inflammatory

process) process)

Causes of an increased ICPCauses of an increased ICP

Conditions Increasing Blood VolumeConditions Increasing Blood Volume obstruction of venous outflow obstruction of venous outflow hyperemia – decreased pO2- inc. CBFhyperemia – decreased pO2- inc. CBF hypercapnea – >pCO2 increases hypercapnea – >pCO2 increases

vasodilation inc CBV , CBF, and ICPvasodilation inc CBV , CBF, and ICP

Causes of an increased ICPCauses of an increased ICP

Conditions Increasing CSF VolumeConditions Increasing CSF Volume increased production(Ch plexus increased production(Ch plexus

papilloma)papilloma) decreased reabsorption of CSF decreased reabsorption of CSF

(meningitis, SAH) (meningitis, SAH) Obstruction to flow of CSF (e.g. aq Obstruction to flow of CSF (e.g. aq

stenosis)stenosis)

THE ENDTHE END