Blood-brain Barrier And Cerebral Spinal Fluid

Question 0

CSF

Answer 0

Clear filtrate from blood that fills ventricles
Produced by vascular fronds-> choroid plexus in all ventricles
Circulates through ventricular system in to 4th ventricle-> 2 lateral and 1 medial exits in to subarachnoid space
Reabsorbed back in to the venous system through arachnoid granulations
Provides correct local environment
Medium of exchange between blood and ECF
150ml-> 500 ml produced each day
Acts as a shockabsorber
Renders brain buoyant

Question 1

Brain ECF

Answer 1

Occupies the ECS
Can’t be quantified as it interacts with CSF, neurones and glial cells
Concs of solute fluctuate with neuronal activity
Influenced by CSF
BBB protects from fluctuations in blood composition and limits entry
Glial cells condition ECF

Question 2

CSF circulation

Answer 2

Lateral ventricles
-> foramina of Monroe
-> third ventricle
-> cerebral aqueduct
-> fourth ventricle
-> two foramina of luschha and one foramina of megendie-> brain stem, cerebellum,cerebral cortex
Or-> subarachnoid space-> arachnoid granulations-> venous sinuses

Question 3

CSF secretion

Answer 3

Two ways:
Ultrafiltration-> across fenestrated capillary wall into ECF beneath the basolateral membrane of the choroid epithelial cells
Chorion epithelial cells secrete fluid in to the ventricles

Question 4

Mechanisms of CSF secretion

Answer 4

Basolateral-> plasma
Na/H exchanger-> H in to plasma, Na absorbed
HCO3/Cl exchanger-> Cl absorbed
Both to excrete CO2 and H2O in to plasma
Apical-> ventricle
3Na/2K -> Na absorbed
Na/2Cl/K-> all absorbed but also all back in
-> NaCl and H2O absorbed
Na gradient used to promote HCO3 accumulation-> Cl influx
Important for neutralising acids produced by glial cells
AQP1-> water through cell

Question 5

CSF composition

Answer 5

Plasma value the CSF value
Water 99% in both
Osmolality 295 in both 
pH 7.41 -> 7.33
Portion 6000-> 20
Glucose 100-> 64
Cholesterol 175-> 0.2 
Na 153-> 147
K 4.7-> 2.9 -> to maintain in hyper polarisation 
Ca 1.3->1.1
Mg 0.6->1.1
Cl 110-> 113

Question 6

Absorption of CSF

Answer 6

Bulk flow via arachnoid granulations -> 500mls per day
Diffusion
Active transport via choroid plexus-> blood vessels covered in pis master but not tight-> potential space-> exchange between CSF and ECF

Question 7

Layers and spaces in brain

Answer 7

Blood
Endothelium 
Basement membrane
ECF
Glial cells
Neurones
Sub ependymal cells
Ependyma
CSF ventricle
Choroid plexus

Question 8

Clinical uses of CSF

Answer 8

Lumbar puncture-> sample-> pathogen detection
Measure of CSF pressure for detection of hydrocephalus, subarachnoid haemorrhage
Spinal block-> anaesthetise spinal nerves distal to the site of application-> intrathecal
Injection into third ventricle-> access to ECF

Question 9

Factors regulating passage across the BBB

Answer 9

Lipid solubility-> increased solubility-> increased access
Degree of ionisation for simple diffusion
-> drugs that are ionised at physiological pH-> less access
Water solubility increases access
Some compounds have special receptors for uptake
Bound to blood protiens-> less access
Freely permeable to water

Question 10

Glucose transport across the BBB

Answer 10

Facilitated transport of monosaccharides
Specific to D glucose
Competitive-> 2-deoxyglucose>glucose> 3,0 methyl glucose > mannose
2-deoxyglucose not metabolised in the brain
GLUT-4 transporters

Question 11

Amino acid transport

Answer 11

Essential amino acids can’t be synthesised in the brain
Phenylamine, leucine, tyrosine, isoleucine, valine, tryptophan, methionine, histidine-> enter as readily as glucose via L-type transporter proteins-> competitive so a high conc of one inhibits absorption of the others
Small neutral amino acids have restricted access as they are non essential, mainly transported out

Question 12

Metabolic barrier in the BBB

Answer 12

Endothelial cells are rich in certain metabolic enzymes such as mono amine oxidase
-> drugs that are metabolised by these enzymes don’t reach the brain
Eg using L-DOPA precursors for Parkinson’s with peripheral DOPA decarboxylase inhibitor

Question 13

BBB disorders

Answer 13

Tumours-> leaky BBB-> increase nutrients-> increased growth
Infiltration-> infection-> increased permeability
Ischaemia-> cellular damage-> increased water-> oedema

Question 14

Non barrier regions

Answer 14

Fenestrated instead of tight junctions-> subfornical organ, OVLT, pineal gland, posterior pituitary, median eminence, area postrema
Allows keep track of periphery
Post pit hormones have direct access to circulation
Median eminence-> oxytocin, vasopressin-> pick up releasing hormones for carriage via pituitary
Area postrema-> chemoreceptor zone-> vomiting
Organum vasculosum of the lamina terminalis (OVLT)-> important for actions of cytokines in periphery

Question 15

Physico-chemical properties of drugs that determines their access to the central nervous system

Answer 15

Penicillin-> usually not lipophilic enough -> inflammation disrupts BBB then can cross
Doperamide-> anti emetic-> access via area postrema
Valproate-> transporters