SAQPhysiologyNeurophysiologyApril 2022 · Blood-brain barrier

Question bank · April 2022 · Physiology

Three structural elements,
five routes across, six functions.

Show the model answerAttempt it first — that is what makes it stick

(a) Anatomical structure 3 marks

What earns the marks3 marks

Introduce itA physiological barrier between the cerebral capillaries and brain extracellular fluid
Name what forms itCapillary endothelium, AND the specialised ependymal cells at the brain-CSF interface
Three endothelial featuresTight junctions, no fenestrations, high mitochondrial content
Beyond the basement membraneAstrocyte foot processes with intercellular clefts

The blood-brain barrier is a physiological barrier between the cerebral capillaries and the extracellular fluid of the brain, providing a favourable environment for nervous tissue by being selectively permeable to substances present in plasma.

ComponentFeatureSignificance
Capillary endotheliumTight junctions (zonulae occludentes) between adjacent cellsReduce the intercellular pore from about 65 Å in other capillary beds to about 8 Å here
Capillary endotheliumAbsence of fenestrationsNo bulk paracellular route
Capillary endotheliumHigh content of mitochondriaSupplies ATP for the carriers and pumps that replace free diffusion
Brain-CSF interfaceSpecialised ependymal cells of the choroid plexusThe second morphological barrier — often omitted
Basement membraneSurrounds the endotheliumStructural support; pericytes embedded within it
Astrocyte foot processesClosely applied beyond the basement membrane, with intercellular clefts between themInduce and maintain the endothelial tight junctions; carry the aquaporin channels handling water movement
PericytesEmbedded in the basement membraneContribute to barrier induction and capillary tone

Commonly lost: Marks were distributed across four elements — the introduction, the two morphological barriers, the three endothelial features, and the astrocyte foot processes. Missing the ependymal cells or the foot processes loses a whole element.

(b) Transfer of substances 4 marks

What earns the marks4 marks · 5 mechanisms

What is permeableO₂, CO₂, water, MW under ~30 kDa with high lipid solubility
What is notLarge, polar or lipid-insoluble substances
Five mechanismsName, explain in a clause, give an example — including pinocytosis
Two specific carriersGlucose on GLUT1 (no ATP); Ca²⁺, Mg²⁺ and Cl⁻ by active transport
MechanismHow it worksATPExample
Simple diffusionDown a concentration gradient, directly through the endothelial cell membrane. Rate depends on lipid solubility, molecular size, ionisation and protein bindingNoO₂, CO₂, water, volatile agents, unionised lipid-soluble drugs such as thiopentone
Facilitated diffusionCarrier-mediated, down a gradient, saturable and stereospecificNoGlucose on GLUT1, which is insulin-independent; amino acids on the large neutral amino acid transporter
Primary active transportAgainst a gradient, hydrolysing ATPYesNa⁺/K⁺-ATPase at the abluminal membrane; P-glycoprotein efflux returning lipid-soluble drugs to blood
Secondary active transportUses the sodium gradient rather than ATP directlyIndirectlyCalcium, magnesium and chloride — how their concentrations in brain ECF and CSF are held independent of plasma
Vesicular transportPinocytosis and receptor-mediated transcytosis. Cerebral endothelium has far fewer vesicles than systemic, so the route is limitedYesInsulin, transferrin

Commonly lost: Two classifications must be the right way round: GLUT1 glucose transport is facilitated diffusion — carrier-mediated and saturable, but down a gradient and needing no ATP — and ATPase transporters are active transport.

(c) Other functions 3 marks

Commonly lost: “Other” means beyond the selective transfer just described in part (b). Repeating transport here earns nothing.

FunctionDetail
Maintaining the constancy of brain extracellular fluidSo neuronal excitability is protected from swings in plasma composition
Enzymatic degradationIn the endothelial cells, effectively preventing entry — monoamine oxidase and dopa decarboxylase
A barrier to microorganismsPreventing entry into the brain
Restricting peripheral immune accessSignalling molecules, antibodies and immune cells
Protection from circulating toxinsWhile allowing metabolic substrates free access
Preventing uncontrolled neurotransmitter and hormone passageCirculating ones into the brain, or centrally released ones into the systemic circulation
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