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65 Cards in this Set

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2 Functions of the BBB
1. To maintain a stable environment for neurons
2. To deliver nutrients to the brain via specialized transporters
How are brain endothelial cells different from general ECs?
(3 things they don't have, 2 they do)
-No fenestrations
-Tight junctions between them
-No intracellular clefts
-No vesicular transport
-Lots of mitochondria
Anatomical basis of BBB:
-Tight junctions unite ECs
-Astrocytic endfeet completely encase ECs
What is the role of astrocytes in the BBB?
-Essential for it to be there
-But not the mechanical basis of it.
What IS the mechanical basis of the BBB?
What can diffuse through the blood brain barrier?
Mechanl basis: tight junctions
-Respiratory gases
-Lipid soluble molecules (drugs of abuse)
3 Types of passage thru BBB:
1. Simple Diffusion
2. Carrier-mediated transport
3. Ion channels
What is special about Glucose and L-dopa passage thru BBB?
Both are relatively LOW in terms of lipid solubility;
BUT both have high extraction rates b/c they have transporters.
What is different about Phenobarbital and Phenytoin passage thru BBB?
Neither is as permeable as you would expect in spite of their lipid solubility - because they don't dissolve in BLOOD (aqueous) very well and Albumin binds and prevents them from crossing into BBB.
What type of transport is the ASC system? What does it transport?
Energy dependent
-transports Ala, Ser, Cys
4 Transport Systems for BBB:
Which are not energy dependent?
-Glucose - nonenergy dependent
-L - nonenergy dependent
-A
-ASC
Features of the L system:
What does it transport?
-Energy independent -facilitated
-Must go down conc gradient
-Large neutral AA with nonpolar side chains
A molecule that uses the L-transport system:
L-dopa
"A" transport system
-Features
-What it transports
-Energy DEPENDENT
-Transports up conc. gradient
-Neutral AA w/ small or POLAR side chains
What glucose transporters are in the brain, and what are their features?
Glut1/Glut3
-12 transmembrane sections
-Energy independent (down gradient)
What are sites that have NO BBB in the brain called?
circumventricular organs
What are the Circumventricular organs? (5)
1. Neurohypophysis
2. Area postrema
3. Subcommissural organ
4. Organum vasculosum
5. Subfornical organ
What is the function of the:
-Neurohypophysis?
-Area Postrema?
-neurohypoph detects osmolarity
-Area postrema is the vomiting center and detects high levels of toxins
What are the different features of ECs in the Circumventricular organs?
-Fenestrated capillaries
-Vesicular transport
-Tanycytes
What are Tanycytes?
Ependymal cells that wall off the circumventricular areas to separate the CSF from the rest of the brain.
What will happen if a hypertonic solution is infused into a brain capillary?
It will cause the capillary to dilate and open the tight junctions -> increased permeability and brkdn of BBB!
4 Things that can cause destruction of the BBB:
1. Trauma
2. Ischemia
3. Meningitis
4. Inflammation
What is the BBB like in brain tumor capillaries?
Absent - a good thing because contrast agents and chemotherapy will have access to kill tumors.
5 results of BBB breakdown:
1. Seizures
2. Hypertension
3. Severe hypercapnia
4. Cerebral vasodilation
5. Capillary distention
Where is CSF found?
Fills ventricles + subarachnoid space
4 Functions of the CSF:
-CUSHIONS brain
-FLOATS (Gives buoyancy) brain
-Provides NUTRIENTS
-Removes BAD WASTE
What does CSF composition affect?
-Cerebral blood flow
-Pulmonary ventilation
Where is CSF produced?
In choroid plexi
Where is choroid plexus located?
In all ventricles
What is the structure of choroid plexus?
Capillary networks surrounded by secretory epithelium.
How are the choroid plexus capillaries different from the surrounding epithelium?
-Capillaries have fenestrations for free permeability to plasma solutes
-Epithelium has tight junctions to limit the permeability
How are plasma solutes taken from the blood stream into CSF?
By active transport across the epithelium surrounding capillaries.
What is the order of bulk flow of CSF?
1. Made in Lateral ventricles
2. Thru interventricular foramin of monro
3. Into 3rd ventricle
4. Thru Aqueduct of sylvius
5. Into 4th ventricle
6. Thru foramen of magendie and foramina of lushke
7. Subarachnoid space, down and around SC/brain surface
8. Thru Arachnoid villi
9. Into dural sinuses
How many times does the CSF completely turnover per day?
4
How much CSF is produced every minute?
1/3 mL
How much CSF is produced every day?
500 ml/day
How much total CSF is in the body at any given time?
140 mL
Where does CSF go from the subarachnoid space?
Down into cortex: virchow-robin spaces extend into the cortex.
Up into arachnoid granulations - to be put into venous sinuses.
What are arachnoid villi and granulations?
Projections of the arachnoid space up into the dural venous sinus system to allow reabsorption of CSF into circ.
What is special about the way Arachnoid granulations function?
They are like one-way valves
How much of CSF passes through arachnoid granulations?
All of it! Nothing is left behind - not filtrated; removal is nonspecific.
How does transport of CSF into dural sinuses occur?
By vesicular transport using Giant Vacuoles
What is the CSF composition similar to?
Plasma
What are major differences about CSF compared to blood plasma?
-Very LOW proteins/amino acids
-Lower: K, Ca, Mg, and Glucose
-Higher: Cl and H+
What is the macroscopic appearance of CSF normally like?
Clear and colorless
What would indicate blood in CSF?
Yellow bloody appearance
What is an increased WBC for CSF?
>5 cells / mm^3
What will an increased WBC CSF look like?
Cloudy
4 Causes of Increased WBCs in CSF:
-Trauma
-Tumor
-Meningitis
-Stroke
What could cause an increased protein in CSF?
-Increased Vascular permeability
-Immunoglobulin production
What would cause a decreased glucose in CSF?
-Bacterial infections
-Decreased Glut1 transporters
What could cause RBCs in CSF?
Hemorrhagic stroke
(or traumatic tap)
Why is it important to monitor CSF pressure?
It is an indication of intracranial pressure (ICP)
What is the normal value for ICP?
5-15 mm Hg
3 methods for CSF pressure measurement:
1. Lumbar puncture
2. Ventricular catheter
3. Subdural/epidural transducer
What is the drawback of lumbar puncture?
It assumes that pressure is equal throughout the neuraxis - might not be altered if there is an obstruction in the brain.
How is Ventricular pressure measured?
By sticking a catheter right in the lateral ventricle - very invasive
What is an epidural/subdural transducer used for?
Measuring brain tissue pressure on a more longterm chronic basis.
What is brain edema?
Increased water content in the brain.
What are 2 types of brain edema?
1. Vasogenic, extracellular

2. Cytotoxic, intracellular
What causes Vasogenic edema, and what is the result?
-Increased EC permeability
-Fluid accumulates along white matter tracts, leaves gray alone
What causes Cytotoxic edema, and what is the result?
Failure of Na/K pump - Na/Water accumulate in cells and causes them to swell - injures cells.
What is hydrocephalus?
Increased CSF volume and pressure
3 types of causes of hydrocephalus:
1. Increased CSF production
2. Obstructed CSF outflow
3. Impaired absorption
2 types of hydrocephalus:
-Noncommunicating
-Communicating
What will be dilated in communicating hydrocephalus?
In noncommunicating?
Comm: subarachnoid space

Noncomm: ventricles prox to plug