Grover - CSF Secretion and Blood-Brain Barrier

Question 1

What two barriers separate the CNS from the body?

What fluids are secreted here?

Answer 1

Blood-CSF Barrier - CSF

Blood-Brain Barrier - Interstitial Fluid (ISF)

Question 2

Where is CSF found?

What secretes it?

Answer 2

Subarachnoid Space

Ventricles

Choroid plexus in lateral and 4th ventricles

Question 3

What membranes is directly responsible for secreting CSF into ventricle space?

What type of junctions are found on apical borders?

Answer 3

Microvilli on Apical surface - expand surface area

Tight Junctions (prevent diffusion)

Question 4

What forms CSF?

What three layers does secretion cross?

Answer 4

Blood

1. Capillary Wall (endothelium)
2. Supporting Layer (between capillar wall and epithelium)
3. Epithelial cell layer

Each layer is potential barrier

Question 5

Endothelial Cell Layer of Choroid Plexus Capillary

(three major)

Answer 5

1. Fenestrations - small gaps between edges, pathways for water, ions, glucose–paracellular transport
2. Pinocytosis
3. Cell Membrane - lipid soluble substances only–transcellular transport

Question 6

Choroid Plexus Capillar Endothelium

What is restricted here?

What is an abnormal finding?

Answer 6

Movement of large protein molecules is RESTRICTED

Presence of protein indicates DISEASE/ABNORMAL condition

Question 7

What moves through the supporting cell layer?

Answer 7

Nothing.

No function in CSF secretion.

Question 8

What creates the barrier in the Epithelial Cell Layer?

How is CSF created here?

Answer 8

Tight Junctions created Blood-CSF barrier

CSF is created by secretion, and its composition is regulated here.

**CSF and plasma composition are DIFFERENT

Question 9

What ions are mainly found in CSF and Plasma?

Answer 9

Na+, Cl- and H20

Question 10

What is the major difference in ions in CSF and Plasma?

Answer 10

CSF has 35% LESS K+, Mg+

CSF has 50% LESS Ca2+

Question 11

What are major differences in CSF and Plasma?

Answer 11

CSF contains less Glucose and NO PROTEIN

Question 12

What are major differences in CSF and plasma?

Answer 12

CSF is MORE STABLE than plasma over time

Stable CSF ion concentration is essential for normal function

Question 13

What drives CSF secretion?

Answer 13

CSF secretion driven by ion transport

Water follows ions by osmosis

Question 14

Transport found in apical membrane?

pH regulation?

Water movement?

Answer 14

Sodium net EXPORT by Na-K-ATPase

Sodium transport by K-Cl Cotransport (anion permeable channels)

Potassium transported BACK by Na-K-ATPase

HCO3- transport by Na+ dependent transporter and diffusion through anion channels

- - -

pH regulated by HCO3- and H+ transport

Water moved through aquaporins

Question 15

Consequences of apical membrane transport?

Answer 15

Na / Cl form bulk ions of CSF

Low K+ in CSF

Ion movement increases ventricle osmotic pressure

Net = Formation of CSF at Apical Surface

Question 16

Basolateral Membrane transport functions?

Answer 16

Maintain intracellular ion concentrations to sustain CSF secretion

Sodium loading by Na+ - HCO3- contransport

Chloride loading by anion exchange

Question 17

What maintains intracellular HCO3- concentration?

What can result if there is deficit in any mechanism loss for ion transport?

Answer 17

Carbonic Anhydrase

Decrease rate of secretion

Question 18

What does entry into CNS require?

Answer 18

Specific Membrane transport in apical or basolateral membrane

or

High lipid solubility

Question 19

Where does CSF fill?

Where does ISF fill?

Answer 19

CSF fills ventricles

ISF fills extracellular spaces

Question 20

What is result of lack of junctions between ependymal cells lining ventricles?

Answer 20

Free Exchange between ventricle and extracellular spaces (free movement in CNS)

Question 21

Source of formation of CSF/ISF?

Answer 21

Choroid Plexus = 60% CSF production

CNS capillaries = 40% CSF production

Question 22

What type of junction is found in CNS capillaries?

What is the result?

Answer 22

CNS capillaries are secretory structures

Tight Junctions create blood-brain barrier

NO pinocytosis, NO paracellular transport

Question 23

What induces capillary specialization?

Answer 23

Trophic factors secreted by astrocyes

Question 24

Major consequences of Blood-Brain and Blood-CSF Barrier?

Answer 24

(+) Protection of CNS from harmful substances

(+) Stable extracellular environment

(-) Excluse potentially beneficial substrances (Drugs, such as L-DOPA for treatment of Parkinson’s)

Question 25

What is strong correlation for substances passage to blood-brain barrier?

What is the result for drugs?

Answer 25

Lipid Solubility

Drugs with high lipid solubility easily enter CNS

Drugs with low lipid solubility exclused from CNS

Question 26

What are some exceptions to the lipid-solubility rule for diffusion into brain?

Answer 26

Cotransport IN substrates = faster

Cotransport OUT substrates = slower

Question 27

Vasogenic Edema

Answer 27

Blood-Brain barrier disruption

Head injury, hemorrhage, infarct, infection

Plasma proteins leak into interstitial space, raise osmotic pressure

***Elevated CSF Protein Concentration***

Question 28

Interstitial Edema

Answer 28

Abnormal CSF Flow

Obstructed flow between ventricles or outflow through arachnoid villi, over secretion of CSF

Increased pressure in ventricles forces CSF into brain space, ventricles EXPAND

Question 29

Cytotoxic Edema

Answer 29

Cellular energy (ATP) Depletion

Caused by disruption of blood/oxygen supple

Failure of active transport, loss of osmotic balance across membrane

Cell Volume EXPANDS

Question 30

Osmotic Edema

Answer 30

Plasma osmolarity too low (water intoxication)

Water drawn across blood-brain, blood-CSF barrier into CSF

Elevated Intracranial Pressure

Question 31

Hydrostatic Edema

Answer 31

Malignant hypertension (sudden large increase in blood pressure

High blood pressure forces fluid from plasma across blood-brain, blood-CSF barriers into CNS

Elevated Intracranial Pressure