Question 12

College Answer

This question has been repeated multiple times. Better answers demonstrated a structured approach to discussing the physiology of CSF dividing concepts into; Formation and Composition, Regulation and Circulation, and Functions of CSF with  the appropriate level of detail.

Discussion

• Cerebrospinal fluid (CSF) is an ultrafiltrate of plasma contained within the ventricles of the brain and the subarachnoid spaces of the cranium and spine.
• Amount:  Approximately 400-600ml/day, or 25ml/hr;
  • At any given time, a normal adult has about 150ml 
  • About 25ml is in the ventricles, and a further 30 ml in the spinal canal
  • The rest is in the subarachnoid space
• Site: three main sources:
  • Choroid plexus within the ventricles (mainly lateral ventricles)
  • Brain interstitial fluid (minor source)
  • Circumventricular organs (very minor source)
• Mechanism: 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 ultrafiltarte, 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 prodction decreases)
• 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
• Function:
  • 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
• Circulation:
  • 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
  • The motor force driving this flow comes from:
    • Constant production at the choroid plexus
    • Arterial pulsation of the central nervous system structures
    • Venous pulsation of the CNS related to the respiratory cycle
    • Constant reabsorption by the arachnoid granulations
• Reabsorption:
  • Reabsorbed at 25ml/hr (CSF secretion rate = reabsorption rate) into the dural venous blood
  • Main sites are 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

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.