Grover - CSF Secretion and Blood-Brain Barrier Flashcards
What two barriers separate the CNS from the body?
What fluids are secreted here?
Blood-CSF Barrier - CSF
Blood-Brain Barrier - Interstitial Fluid (ISF)
Where is CSF found?
What secretes it?
Subarachnoid Space
Ventricles
Choroid plexus in lateral and 4th ventricles
What membranes is directly responsible for secreting CSF into ventricle space?
What type of junctions are found on apical borders?
Microvilli on Apical surface - expand surface area
Tight Junctions (prevent diffusion)
What forms CSF?
What three layers does secretion cross?
Blood
- Capillary Wall (endothelium)
- Supporting Layer (between capillar wall and epithelium)
- Epithelial cell layer
Each layer is potential barrier
Endothelial Cell Layer of Choroid Plexus Capillary
(three major)
- Fenestrations - small gaps between edges, pathways for water, ions, glucose–paracellular transport
- Pinocytosis
- Cell Membrane - lipid soluble substances only–transcellular transport
Choroid Plexus Capillar Endothelium
What is restricted here?
What is an abnormal finding?
Movement of large protein molecules is RESTRICTED
Presence of protein indicates DISEASE/ABNORMAL condition
What moves through the supporting cell layer?
Nothing.
No function in CSF secretion.
What creates the barrier in the Epithelial Cell Layer?
How is CSF created here?
Tight Junctions created Blood-CSF barrier
CSF is created by secretion, and its composition is regulated here.
**CSF and plasma composition are DIFFERENT
What ions are mainly found in CSF and Plasma?
Na+, Cl- and H20
What is the major difference in ions in CSF and Plasma?
CSF has 35% LESS K+, Mg+
CSF has 50% LESS Ca2+
What are major differences in CSF and Plasma?
CSF contains less Glucose and NO PROTEIN
What are major differences in CSF and plasma?
CSF is MORE STABLE than plasma over time
Stable CSF ion concentration is essential for normal function
What drives CSF secretion?
CSF secretion driven by ion transport
Water follows ions by osmosis
Transport found in apical membrane?
pH regulation?
Water movement?
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
Consequences of apical membrane transport?
Na / Cl form bulk ions of CSF
Low K+ in CSF
Ion movement increases ventricle osmotic pressure
Net = Formation of CSF at Apical Surface
Basolateral Membrane transport functions?
Maintain intracellular ion concentrations to sustain CSF secretion
Sodium loading by Na+ - HCO3- contransport
Chloride loading by anion exchange
What maintains intracellular HCO3- concentration?
What can result if there is deficit in any mechanism loss for ion transport?
Carbonic Anhydrase
Decrease rate of secretion
What does entry into CNS require?
Specific Membrane transport in apical or basolateral membrane
or
High lipid solubility
Where does CSF fill?
Where does ISF fill?
CSF fills ventricles
ISF fills extracellular spaces
What is result of lack of junctions between ependymal cells lining ventricles?
Free Exchange between ventricle and extracellular spaces (free movement in CNS)
Source of formation of CSF/ISF?
Choroid Plexus = 60% CSF production
CNS capillaries = 40% CSF production
What type of junction is found in CNS capillaries?
What is the result?
CNS capillaries are secretory structures
Tight Junctions create blood-brain barrier
NO pinocytosis, NO paracellular transport
What induces capillary specialization?
Trophic factors secreted by astrocyes
Major consequences of Blood-Brain and Blood-CSF Barrier?
(+) Protection of CNS from harmful substances
(+) Stable extracellular environment
(-) Excluse potentially beneficial substrances (Drugs, such as L-DOPA for treatment of Parkinson’s)
What is strong correlation for substances passage to blood-brain barrier?
What is the result for drugs?
Lipid Solubility
Drugs with high lipid solubility easily enter CNS
Drugs with low lipid solubility exclused from CNS
What are some exceptions to the lipid-solubility rule for diffusion into brain?
Cotransport IN substrates = faster
Cotransport OUT substrates = slower
Vasogenic Edema
Blood-Brain barrier disruption
Head injury, hemorrhage, infarct, infection
Plasma proteins leak into interstitial space, raise osmotic pressure
***Elevated CSF Protein Concentration***
Interstitial Edema
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
Cytotoxic Edema
Cellular energy (ATP) Depletion
Caused by disruption of blood/oxygen supple
Failure of active transport, loss of osmotic balance across membrane
Cell Volume EXPANDS
Osmotic Edema
Plasma osmolarity too low (water intoxication)
Water drawn across blood-brain, blood-CSF barrier into CSF
Elevated Intracranial Pressure
Hydrostatic Edema
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
