Cerebral Circulation — Blood–Brain Barrier

Current · V5 (2025) → H2.iv Historical · V4 (2023) → K1.iii 4 exam appearances

2025A Q05

Exam question

With respect to the blood brain barrier (BBB), outline the following: (a) the structure (15% of marks). (b) its function (25% of marks). (c) the mechanisms by which substances, including drugs move across the BBB and explain how this is determined or regulated (45% of marks). (d) the regions that lie outside the BBB and their purpose (15% of marks).

CICMWrecks answer

Master answer

Blood brain barrier

Anatomical and chemical partition separating the intravascular space from CNS interstitial space

Structure

Mechanical barrier
- Endothelial cells
  - Tight junctions between cells formed by membrain proteins (e.g. occludin) prevents paracellular flow
  - Lack fenestrations
  - Lack transcellular pathways such as vescicles
  - Selective transport proteins (e.g. GLUT, various amino acid transporters)
- Pericytes embedded in basement membrane
- Astrocyte end feet
  - Supportive role for endothelium
  - Aquaporin regulation
Physiological barrier
- Enzymatic inactivation
  - Enzymtes within endothelial cells metabolise substances absorbed from capillary lumen
    - Monoamine oxidase
    - Cholinesterase
    - Aminopeptidase and endopeptidase
- Efflux pumps
  - Substances that are absorbed across the luminal capillary membrane may be pumped back into capillary lumen by efflux pumps
    - P-Glycoprotein
    - ABC-Transporter
Areas of brain outside BBB
- Subfornical organ
- Organum Vasculosum Lamina Terminalis
- Pituitary
- Area postrema

Function

Regulate uptake of nutrients and electrolytes into brain
Regulate migration of leukocytes and inflammatory responses in the brain
Buffer brain parenchyma and interstitium from fluctuations in blood
Prevent toxins and pathogens entering brain
Some substances (such as water) pass BBB readily. These are characterised by:
- Small molecular weight
- Lipophilic (thiopentone)
- Uncharged (e.g. atropine vs. glycopyrollate)
- Poorly protein bound

Sakurai 2016

Answer by Sakurai

Past papers

Exam appearances

4 appearances

Exam	Exact exam wording	Candidate success
2025A Q05	With respect to the blood brain barrier (BBB), outline the following: (a) the structure (15% of marks). (b) its function (25% of marks). (c) the mechanisms by which substances, including drugs move across the BBB and explain how this is determined or regulated (45% of marks). (d) the regions that lie outside the BBB and their purpose (15% of marks).	24%
2015A Q03	Describe the structure and function of the blood brain barrier	33%
2012B Q12	Describe the blood brain barrier (50% of marks). What characteristics does a drug need to effectively penetrate the blood brain barrier? (50% of marks)	41%
2009B Q08	Describe the blood brain barrier. (50% of marks) What characteristics does a drug need to effectively penetrate into the central nervous system? (50% of marks)	22%