Blood-brain Barrier And Cerebral Spinal Fluid Flashcards Preview

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Flashcards in Blood-brain Barrier And Cerebral Spinal Fluid Deck (16)
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Brain ECF

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

1

CSF

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

2

CSF circulation

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

3

CSF secretion

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

4

Mechanisms of CSF secretion

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

5

CSF composition

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

6

Absorption of CSF

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

7

Layers and spaces in brain

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

8

Clinical uses of CSF

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

9

Factors regulating passage across the BBB

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

10

Glucose transport across the BBB

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

11

Amino acid transport

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

12

Metabolic barrier in the BBB

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

13

BBB disorders

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

14

Non barrier regions

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

15

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

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