Blood brain barrier Flashcards
Name the brain areas lacking a BBB
Circumventricular organs
- Area postrema- chemoreceptor- vomiting
- Post pituitary- hormones released have direct access to circulation
- Median eminence- oxytocin, vasopression. Pick up releasing hormones for carriage to the ant pituitary
- OVLT- organ vasculosum of lamina termalis- actions of cytokines in the periphery- fever
Describe the effects of tumours on the BBB
Leaky BBB
increased nutrients, increased growth
Describe the effect of infiltration
Infection
Increased antibiotic permeability
Describe the effect of ischaemia
Cellular damge
Increased water, oedema
Why can’t dopamine cross the BBB?
Ionised at ph 7.4
Which factors regulate passage through the BBB?
Lipid solubility increases, access increases
Plasma protein binding– to large
Ionisation at ph 7.4–less acess
Name 3 lipid soluble molecules
L leucine
D glucose
L DOPA
Why can’t anti epileptics cross?
Plasma protein bound– lower uptake
How is glucose transported?
D glucose transported via GLUT1, not metab by brain, taken up mark cell activity- PET
Essential aa transported, not transporters
Define BBB
CNS needs ultrastable environment Altered if ECF composition is altered Morphological factors and mechanisms reg transport across brain capillary endothelial cells Tight junctions between endo cells Restricts mW>2000 eg proteins
Describe the clinical use of CSF
Spinal block to anesthesise spinal nerves distal to site of application- intrathecal drug application
Routine procedure
Injection into third ventricle, unlimited access to ECF so neurones and glia. not routine
Describe lumbar puncture
Sampling of CSF for detection of pathogens eg MS, meningitis
Measure CSF pressure for detection of hydrocephalus, sub arachnoid haemorrhage
Routine clinical procedure L3-5
List the routes of drainage of CSF
Bulk flow via arachnoid villi
Diffusion- vascular epi
AT- choroid plexus eg weak organic acids
Describe the composition of CSF
Low protein, cholesterol, K+
Describe the mechanism of CSF secretion
Basolateral- neutralise weak acids from CNS- H+/Na+ in, HCO3- accum, leaves, Cl- in
Apical membrane- Na+ out/K+ in
HCO3- and CL- leave- KCC4 transport
AQP1- water transporter
Describe the two processes of CSF secretion
- Choroid epi cells secrete fluid into ventricles
- Ultrafiltration of plasma across fenestrated capillary wall into ECF beneath basolateral membrane of choroid epi cell
Outline CSF movements
Lateral ventricles- cortex Foramina of Monroe 3rd ventricle- Thalamus Cerebral aqueduct of Sylvius Fourth ventricle- brain stem Two foraminae of Luschka and Magendie Subarachnoid space
List 8 functions of cerebrospinal fluid
Cushion, shock absorber
Appropriate environment for glial cells/neurones
Exchange medium- ECF and blood
Waste removal- drugs, NT, metabolites
Fills ventricles- thin layer, around brain and SC
Interface between brain and peripheral endo functions
150 mls, 500mls a day
CSF secretion pushes CSF- SA space
Describe the blood CSF barrier
CSF- filtrate of blood made in choroid plexus of ventricles- around brain and sc
Arachnoid gran-CSF- venous sinuses- systemic circulation
Nutrient transfer and waste removal
Describe ECF
Interacts with CSF, neuronal cells, glia. Solute conc fluctuates with neuronal activity
CSF affects composition
BBB prodects ECF from fluctuations in conc, limit compound entry
Glial cells (astrocytes) condition ECF