Blood Brain Barrier and intracranial pressure Flashcards
Which ion is at higher concentrations in the CSF than blood?
Sodium ions
The main difference of the choroid epithelia compared to other epithelia is
The apical location of Na+, K+ ATPase, and Na+, K+, 2Cl- cotransporter, and high CA activity. In normal epithelia, only Cl- is on the apical side.
What are 3 drugs that inhibits CSF secretion by the choroid plexus?
Acetazolamide, Bumetanide, Furosemide
Acetazolamide
Decreases CSF secretion by inhibiting the carbonic anhydrase enz
Furosemide
Blocks K-Cl cotransport by KCC3
Bumetanide
Blocks the Na-K-2Cl cotransporter of the choroid plexus (BCSFB)
difference between the choroid plexus blood-csf barrier and the blood brain barrier
The BCSFB has fenestrated capillaries and ependymal cells that produce CSF.
The BBB has tight junctions in their endothelial cells and don’t cell much pass. They also have astrocytic foot processes.
Absorption of CSF
Arachnoid villi, massive vacuoles
Venous thrombosis
E.g. cerebral venous thrombosis (CVT) can increase intracranial pressure, but rarely cause hydrocephalus
Glymphatic system
The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular channels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system, which is more active during REM sleep and may be involved with Alzheimer’s and depression.
What is the pathological change in the glympathic system that causes Alzheimer’s or normal pressure hydrocephalus?
Altered AQP4 expression
Obstruction of CSF causes
Dilation of the venticular system proximal to the obstruction with profound effect on intracranial pressure.
Choroid plexus papilloma
causes increased production of CSF, and causes communicating hydrocephalus
Normal pressure hydrocephalus
Adam’s triad: Gait disturbances, dementia, urinary incontinence. Can be cured. Probable etiology is decreased reabsorption of CSF through arachnoid granulations.
The CSF tap test, also called a large-volume
lumbar puncture, involves the
withdrawal of
40–50 ml of CSF by means of lumbar puncture.
Symptomatic improvement after the CSF tap test means that
Increased likelihood of a favorable
response to shunt placement (positive predictive value 73–100%).
Ventriculoperitoneal Shunt
Shunt from lateral ventricles into peritoneal cavity, helps with normal pressure hydrocephalus
Virchow-Robin space
Space betweem the capillaries in the brain and the glial endfeet
Intrathecal drug delivery applications
Chemotherapy (methotrexate, cystosine arabinoside, meningeal spread - leukemia), spinal anesthesia, steroids for pain relief, antisense oligonucleotides
Clinical application of CNS immune privilege
Nerve cell transplant e.g. ventral midbrain cells can survive up to 14 years in PD patients
4 possible theories behind how CNS has immune privilege
- BBB, 2. Lack of lymphatic drainage, 3. Lack of potent APCs, 4. Presence of immunosuppressive factors e.g. TGF-beta, FASL, ganglioside, PDL1
Blood brain barrier
- Endothelial cells with TIGHT JUNCTIONS 2. Continuous capillaries 3. Foot processes of astrocytes (not a barrier)
Two regions in the brain lacking BBB (with fenestrated capillaries)
the area postrema, posterior pituitary area
Which cells can release vasoactive compounds directly to SMCs located around blood vessels near the surface of the brain?
- Excitatory neurons 2. Interneurons 3. Astrocytes
Extravasation process
Occurs due to inflammation, CNS infection.
Causes upregulation of
1. ICAM1
2. VCAM1
Why can penicillin or other drugs sometimes be used to fight infections in the brain?
Extravasation or cytokine release after CNS infection allows leakier blood vessels
Which part of the brain has lymphatic drainage?
Meninges, or inside the dura mater
What molecules can pass the BBB?
Lipid soluble, negatively charged > positively charged, hypoxia, injury or inflammation decreases Bbb resistance
Adsorptive-mediated transcytosis
Allows positively charged molecules to pass in vesicles e.g. albumin, other plasma proteins
Carrier-mediated transcytosis
Glucose, neutral amino acids, purines e.g. adenosine, monocarboxylic acids
Receptor-mediated transcytosis
Specific receptor allows Insulin, transferrin to enter the CNS
Cell migration through the BBB
some viruses use cell migration in the brain to enter the CNS
Transcellular lipophilic pathway
Lipid soluble agents esp. free fatty acids can pass into the brain
Amino acids transport into the CNS
L system – large neutral amino acid, Na+ independent, facilitative transporter
A system – glycine, energy-dependent Na+ dependent
ASC system alanine, serine, cysteine
energy-dependent Na+ dependent
Some drugs do not work as effectively on the brain because
- They cannot cross the BBB 2. They are actively transported out
Epileptic patients have … drug resistance
Increased, due to multidrug transporter overexpression
When is the BBB functional and working?
Since the first few days of NS development.
The best way to see brain tumors is to use …
T2 weighted MRI or FLAIR image
Vasogenic edema
extravasation and extracellular accumulation of fluid into the cerebral parenchyma caused by disruption of the blood-brain barrier (BBB)
Cytotoxic edema
intracellular accumulation of fluid and Na+ resulting in cell swelling
How to treat cytotoxic edema?
Give hypertonic saline solution e.g. mannitol to draw water out of the brain and into the blood
How to treat vasogenic edema?
Steroids, to decrease BBB leakiness
Normal ICP
0-15 mmHg
Average intracranial volume
1700 mL
Cerebral perfusion pressure
CPP = MAP - ICP
MAP
= 2/3 of diastolic + 1/3 of systolic
Normal CPP
70-100 mmHg
CBF, cerebral blood flow
750 mL/min, higher need in gray matter, highest in neurohypophysis, used to maintain neurotransmitter homeostasis
Ischemia values
CPP < 50 mmHg
Hypercapnia, defined as an elevation in the arterial carbon dioxide tension, causes…
Increased CBF, decreased plateau phase (less autoregulation ability to maintain CBF)
Acute mountain sickness AMS
Acute mountain sickness is caused by reduced air pressure and lower oxygen levels at high altitudes. The faster you climb to a high altitude, the more likely you will get acute mountain sickness. The best way to prevent altitude illness is to ascend gradually.
Biphasic nature of brain tumors
There is a compensation phase, where the brain tumor does not produce symptoms. Then the decompensated phase seems like a sudden onset of symptoms.
Cushing’s triad in increased ICP due to brain tumor (end-stage, decompensation stage)
- Systolic pressure increases (diastolic decreases, increased Pulse pressure)
- Bradycardia
- Tachypnea, Cheyne-Stokes (waxing and waning in cycles)
Common causes of I-ICP
• Vascular abnormalities: AV malformations, aneurisms, stroke
• Diffuse cerebral ischemia: Closed head trauma, shaken baby, vasospasm
• CNS infections
• Tumors
• Trauma
• Obstruction of CSF flow
I-ICP diagnosis
- Papilledema
- Nuchal rigidity
- Lumbar puncture (limited indications due to risk of brain herniation, should do brain imaging first)
ICP monitoring can show A, B, C Lundberg waves
A waves are pathological plateau waves. Means loss of autoregulation.
How does the choroid plexus create CSF?
the BCSFB
What is the turnover rate of CSF?
3-5 times per day
0.35 ml/min, 500 ml/day
