Question 6

College Answer

To achieve a pass in this question, candidates needed to state where and how CSF was
formed, where it flows to after formation followed by a list of its functions. Additional
credit was given for knowledge of rates of production and basic CSF composition. The fact
that CSF production is constant whilst its absorption is pressure dependant was often
overlooked. Thus candidates were expected to mention that there is ~ 150 ml of CSF in the
adult, half within the cranium; about 60-70% of the CSF is formed by the choroid plexuses,
the remaining 30-40% by the cerebral vessels lining the ventricular walls; in humans the
CSF turns-over ~ 4 times/day; composition is essentially brain ECF; brain ECF normally
occupies ~ 15% of brain volume; CSF flows out through the foramina of Magendie and
Luschka and is absorbed through the arachnoid villi into the cerebral venous sinuses;
absorption, being largely by bulk flow, is proportional to ventricular pressure [at normal
pressure ~ 7.0-18.0 cmH2O (mean ~ 11), filtration = absorption, when pressure falls below
~ 7 cmH2O absorption ceases] and CSF Functions [buoyancy, constant metabolic
environment, buffers CSF against rapid plasma changes in K+, Ca++, Mg++, transport of
chemical messengers, sink for waste disposal].
A number of candidates embarked on long discussions of how CSF pH affects physiology
to the exclusion of what was asked for in the question. Many answers did not adequately
cover the three components asked for in the question.
Syllabus: CNS 2d
Reference Text: Guyton Chp 61

Discussion

• 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)
• Production: 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

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.