Blood CNS Barriers in Homeostasis Flashcards
Definition of pericyte
Cells that surround the brain capillaries and trap large macromolecules that have escaped from the lumen
Definition of simple diffusion
Diffusion via paracellular clefts
Definition of passive diffusion
Diffusion through the cell
Definition of the partition coefficient
Increased Pc => increased lipophilicity and uptake into BBB
Where is the blood brain barrier
At the level of the brain capillaries
Describe the vascular supply of the brain
2 carotid arteries
2 vertebral arteries
Circle of Willis at base of brain => pial arteries above pia mater
Penetrating arteries, branch off and penetrate brain tissue but not into pia mater
Penetrating arterioles
Intracerebral arterioles
Capillaries
Describe the brain capillary density in the brain
Why is this adaptation necassery
2500-3000mm3
- no brain cell is 1-2 cell widths away from a capillary
- v efficient for diffusion
Describe the structure of capillaries in the neurovascular unit
Monolayer of endothelial cells that form the paracellular cleft
Surrounded by pericytes and basal lamina
Basal lamina surrounded by end feet of astrocytes, neurones
Oligodendrocytes surround neurones
Describe the structure of the astrocytes within the brain
End feet of astrocytes form a perivascular sheet around the endothelium
Layer found under the pia mater and forms the glia limitans
What are the 5 functions of astrocytes
- energy and nutrient support of neurons
- ion and water homeostasis
- termination of synaptic activity
- maintenance of blood brain barrier
- sense [O2], [CO2] in tissue fluid and regulate breathing
What 2 structures found in brain capillaries to limit paracellular movement
Why are they present
Adherens junctions
- adhesion molecules
- cadherin, both attach to catenin => actin cytoskeleton
Tight junction
- claudin, occludin
- adhesion molecules both attach to zones occludentes => actin cytoskeleton
Limits substance movement between cells => stops simple diffusion
Describe passive diffusion through the blood brain barrier
How does partition coefficient relate to diffusion
Small lipid molecules and blood gases passively diffuse due to lipid bilayer
Increased partition coefficient => increased lipophilicity and uptake into BBB
Describe the diffusion of the drugs
- morphine
- codeine
- heroin into the BBB and their actions
Morphine => not lipophilic, can’t enter
Codeine => lipophilic, can enter
Heroin => very lipophilic, can enter
Heroin in metabolised to morphine which can’t escape BBB with a long half life
Describe the 2 main types of transporter in the lipid bilayer
What are the functions of each main type
Solute carrier transporters (SLC)
- faciliated diffusion
- 2ndary AT
GLUT1 for D glucose
carriers for neutral AA, acidic AA, basic AA
ATP binding cassette (ABC)
- efflux transporter out of brain
- 1ary AT
P-glycoprotein
Describe the polarity of the AA transporters
Not all expressed on both sides of the membrane
Some cotransported with Na
Describe the structure of P-glycoprotein
Describe the drug properties that will be impacted by P-glycoprotein
Transmembrane domain
Binding sites in lipophilic region of bilayer
Drugs must be lipophilic to enter cell but will be extruded back into the blood
Describe the process of non selective fluid phase endocytosis
Any molecule nearby the luminal membrane => vesicle => cytoplasm
Contents released on basal side
Describe the process of selective receptor mediated transcytosis
What molecules are transported this way
Specific molecules bind to receptors
Triggers vesicle formation and carried to the other side
Receptor releases molecule on the other side
Insulin
Transferrin
Describe the process of selective adsorptive transcytosis
What molecule is transported this way
+ve charged molecule attracted to -ve glycocalyx
Triggers vesicle formation and carried to the other side
+ve charged molecule released on the other side
Albumin
Describe the metabolic barrier on the BBB via enzyme systems
What are the 2 main enzymes found here
How are substrates here generally processed
High [monoamine oxidase], [DOPA decarboxylase] embedded within membrane
Substrates hydrolysed and enter cell
- either extruded out via efflux transporters
- metabolized so it can’t pass through basal membrane
What are the 4 functions of the BBB
Why is this important
Control molecule influx => brain ISF
Supplies brain with essential nutrients
Mediates efflux of waste
Restricts ionic/fluid movement
Protects brain from ionic fluctuations present in plasma
Stabilises ISF so conditions are optimal for neuronal function
What are the main 3 structures involved in the blood CSF barrier
Choroid plexus in all 4 ventricles
Barrier formed by arachnoid membrane
What is the function of the choroid plexus
Produce CSF
Synthesizes polypeptides => help regulate brain ISF
Describe the structure of the choroid plexus
No tight junction in paracellular cleft between endotheium => leaky
Extracellular fluid space between endothelium and epithelium
Monolayer of choroid plexus epithelial cells form blood CSF barrier due to tight junctions
Tight junctions on CSF side but not as tight as in BBB
Describe how CSF is excreted
NaKATPase on CSF side of epithelium
2ndary AT of NaH and HCO Cl
K, Cl, HCO3 leave via channels and transporters
Na movement followed by H2O via AQ1
Describe the pathway of CSF flow in the brain
Released by choroid plexus => ventricles => sub arachnoid space
Moves by hydrostatic pressure differences (bulk flow)
How does CSF leave the CNS
Why can’t CSF leave via the arachnoid mater
Subarachnoid space => arachnoid villus (1 way valve) => sup sagittal sinus
Can’t leave via the arachnoid mater due to tight junctions between overlaping cells
What volume of fluid is found in the CSF and the ISF
What is the rate of fluid production in both the CSF and ISF
Total CSF = 140
Rate of fluid production = 350ul/min
Total ISF = 280
Rate of fluid production = 7ul/min
What are the circumventricular organs
What are the 2 types and what do they do
Capillaries here have no tight junctions => v leaky
Found in the ventricles
Sensory
-senses changes in the blood
Neurohaemal secretory
-secretes substances into the blood
Describe how Alzheimers can occur
Amyloid B removal process from the brain is damaged
-receptor mediated endocytosis can’t occur
