Question 16

College Answer

Most candidates answered the question well. The most common mistake was incorrect CSF
composition. Better answers also discussed raised ICP and CSF’s role in the compensation 
for raised ICP.

Discussion

• Formation:  
  • 400-600ml/day, by highly regulated ultrafiltration and active secretion
  • Ultrafiltrate of plasma is formed by the fenestrated choroidal capillaries
  • It collects in the choroid interstitial space
  • Ions are actively transported out of this ultrafiltrate, and into the CSF:
    • Sodium is actively secreted from the apical membrane (Na/K/ATPase)
    • Carbonic anhydrase also provides H⁺ to power Na/H⁺ exchange at the basal membrane
    • The sodium gradient created and maintained in this way is then used to co-transport HCO₃- and CL^-  into CSF
  • This creates an osmotic gradient which pulls water across the membrane through aquaporin channels
  • This process is disconnected from ultrafiltration, i.e. CSF production is constant and is not pressure-dependent (though at low CPP, <55 mmHg, CSF production decreases)
• Absorption:
  • Absorbed at 25ml/hr (CSF secretion rate = reabsorption rate) into the dural venous blood, mainly from arachnoid granulations
  • Driving force is hydrostatic gradient between CSF and venous blood
  • Thus, CSF reabsorption stops when CSF pressure is less than ~ 7 cm H₂O
• Distribution
  • Did the examiners mean "where is it?" ..Well: 150ml of CSF is distributed evenly between the cranium and the spine, with about 25ml in the lateral ventricles, and the majority of it in the subarachnoid spaces.
  • Or did they mean circulation? In which case:
    • ​​​​​​​Out of the choroid plexus on the floor of the lateral ventricles
    • Through the foramen of Munro into the third ventricle
    • Through the Aqueduct of Sylvius, into the fourth ventricle
    • From the fourth ventricle, into the cisterna magna via the lateral foramina of Luschka and then up to the basilar cisterns around the pons, and then to the rest of the cortex
    • Or, from the fourth ventricle, via the medial foramen of Magendie, down to the spinal subarachnoid space
    • It is then reabsorbed from the subarachnoid space
• Role:
  • ​​​​​​​​​​​​​​Barrier function (the blood-CSF barrier)
  • Chemical stability and waste removal
  • Buoyancy and mechanical cushioning of the CNS
  • Hydraulic pressure buffering of ICP with arterial pulse and respiration
• Composition:
  • ​​​​​​​​​​​​​​CSF contains minimal protein (~0.2g/L)
  • CSF sodium potassium and calcium are slightly lower than plasma
  • CSF chloride CO2 and bicarbonate are higher than plasma
  • CSF glucose is about 2/3rds of the plasma value

Sakka, Laurent, Guillaume Coll, and Jean Chazal. "Anatomy and physiology of cerebrospinal fluid." European annals of otorhinolaryngology, head and neck diseases 128.6 (2011): 309-316.

Segal, Malcolm B. "The choroid plexuses and the barriers between the blood and the cerebrospinal fluid." Cellular and molecular neurobiology 20.2 (2000): 183-196.

Brown, P. D., et al. "Molecular mechanisms of cerebrospinal fluid production." Neuroscience 129.4 (2004): 955-968.