K1iv / 15A03: Structure + Function of BBB

15A03: Exam Report

Describe the structure and function of the blood brain barrier.

33% of candidates passed this question.

There was general lack of understanding of the conceptual framework of the blood brain barrier (BBB) and its function. To attain a pass, candidates were required to describe the concept of BBB as a physical and a transport barrier, describe the role of tight junctions and glial cells and identify important barrier functions with some examples of things commonly transported across or excluded.

K1iv / 15A03: Describe the structure and function of the BBB

  • BBB = highly regulated interface which separates the CNS from the blood

Function of the BBB

  1. CNS homeostasis → provides a stable environment for neurons
  2. Protect brain from toxins
  3. Tight control of electrolytes
  4. Protects brain from transient ∆BGL
  5. Prevents release of central NT into systemic circulation

Structure of BBB

Structure of BBB

Endothelial Cells

  • No fenestrations
  • Have TIGHT JUNCTIONS
  • Prevents passage of molecules from blood → brain
  • Multiple mitochondria → large amounts of Active Transport

Astrocytes

  • Contain many enzymes which metabolise substances before they can reach BBB

Drugs Metabolised by BBB

  • MAO → breaks down dopamine & NA
    • ∴we can’t give dopamine to Rx PD
    • We must give L-DOPA which is then converted to dopamine
  • Cholinesterases → metabolise ester Las

Substance Regulation

(Small + lipid soluble)

  • CO2
  • O2
  • EtOH
  • Nicotine
  • H2O

↓

PASS

Cannot Pass

  • Electrolytes
  • Proteins
  • Ab’s
  • Hydrophyllic

BBB Transport

  • Diffusion: CO2, O2, EtOH, H2O
  • Facilitated: amino acids, glucose (GLUT – 1)
  • Receptor mediated endocytosis (Insulin)
  • Paracellular transfer

Circumventricular Organs

  • Area where BBB is absent

↓

  • Have neuroendocrine role ∴need access to systemic circulation
  • Vomiting centre (area postrema)
  • Pineal gland (secretes melatonin)
  • Neurohypophysis of the PPG (releases oxytocin + ADH)

Disruption to BBB

  • Inflammation
  • Oedema
  • HTN (stretching & weakening tight junctions)
  • Epilepsy (↑BP → weakens TIGHT JUNTIONS → restored 1hr post seizure)

Drugs to Penetrate CNS

Fick's Law
  • Solubility = required to be lipid soluble. CNS covered by 2 layers of membrane → BBB & PM of neurons
  • Size = smaller = better. Must be <400Da
  • Ionisation = penetration is in the UNIONISED FORM

∴ weak acids penetrate CSF better

  • CNS Metabolism = drugs metabolised in CNS will create a gradient for diffusion
  • Inflammation = loss of BBB integrity will ↑SA available & ↑rate of drug diffusion e. antibiotics for meningitis