Cerebrospinal Fluid

Cerebrospinal fluid 1

Cerebrospinal fluid

Vials containing human cerebrospinal fluid.

Cerebrospinal fluid (CSF) is a clear colorless bodily fluid found inthe brain and spine. It is produced in the choroid plexus of the brain. Itacts as a cushion or buffer for the cortex, providing a basic mechanicaland immunological protection to the brain inside the skull, and itserves a vital function in cerebral autoregulation of cerebral bloodflow.

The CSF occupies the subarachnoid space (the space between thearachnoid mater and the pia mater) and the ventricular system aroundand inside the brain and spinal cord. It constitutes the content of theventricles, cisterns, and sulci of the brain, as well as the central canalof the spinal cord.

FunctionsCSF serves four primary purposes:1. Buoyancy: The actual mass of the human brain is about 1400grams; however, the net weight of the brain

suspended in the CSF is equivalent to a mass of 25grams. The brain therefore exists in neutral buoyancy, whichallows the brain to maintain its density without being impaired by its own weight, which would cut off bloodsupply and kill neurons in the lower sections without CSF.

2. Protection: CSF protects the brain tissue from injury when jolted or hit. In certain situations such as autoaccidents or sports injuries, the CSF cannot protect the brain from forced contact with the skull case, causinghemorrhaging, brain damage, and sometimes death.

3. Chemical stability: CSF flows throughout the inner ventricular system in the brain and is absorbed back into thebloodstream, rinsing the metabolic waste from the central nervous system through the bloodbrain barrier. Thisallows for homeostatic regulation of the distribution of neuroendocrine factors, to which slight changes can causeproblems or damage to the nervous system. For example, high glycine concentration disrupts temperature andblood pressure control, and high CSF pH causes dizziness and syncope. To use Davson's term, the CSF has a"sink action" by which the various substances formed in the nervous tissue during its metabolic activity diffuserapidly into the CSF and are thus removed into the bloodstream as CSF is absorbed.[1]

4. Prevention of brain ischemia: The prevention of brain ischemia is made by decreasing the amount of CSF in thelimited space inside the skull. This decreases total intracranial pressure and facilitates blood perfusion.

HistoryVarious comments by ancient physicians have been read as referring to CSF. Hippocrates discussed "water"surrounding the brain when describing congenital hydrocephalus, and Galen referred to "excremental liquid" in theventricles of the brain, which he believed was purged into the nose. But for some 16 intervening centuries of ongoinganatomical study, CSF remains unmentioned in the literature. This is perhaps because of the prevailing autopsytechnique, which involved cutting off the head, thereby removing evidence of the CSF before the brain wasexamined. The modern rediscovery of CSF is now credited to Emanuel Swedenborg. In a manuscript writtenbetween 1741 and 1744, unpublished in his lifetime, Swedenborg referred to CSF as "spirituous lymph" secretedfrom the roof of the fourth ventricle down to the medulla oblongata and spinal cord. This manuscript was eventuallypublished in translation in 1887.


Albrecht von Haller, a Swiss physician and physiologist, Avery Kinsey, made note in his 1747 book on physiologythat the "water" in the brain was secreted into the ventricles and absorbed in the veins, and when secreted in excess,could lead to hydrocephalus.Francois Magendie studied the properties of CSF by vivisection. He discovered the foramen Magendie, the openingin the roof of the fourth ventricle, but mistakenly believed that CSF was secreted by the pia mater.Thomas Willis (noted as the discoverer of the circle of Willis) made note of the fact that the consistency of the CSFis altered in meningitis.In 1891, W. Essex Wynter began treating tubercular meningitis by tapping the subarachnoid space, and HeinrichQuincke began to popularize lumbar puncture, which he advocated for both diagnostic and therapeutic purposes. In19th and early 20th century literature, particularly German medical literature, liquor cerebrospinalis was a term usedto refer to CSF.In 1912, William Mestrezat gave the first accurate description of the chemical composition of the CSF. In 1914,Harvey W. Cushing published conclusive evidence that the CSF is secreted by the choroid plexus.

Circulation

MRI showing pulsation of CSF

CSF is produced in the brain by modified ependymal cells in thechoroid plexus (approx. 50-70%) and the remainder is formed aroundblood vessels and along ventricular walls. It circulates from the lateralventricles to the foramina of Monro (Interventricular foramina), thirdventricle, aqueduct of Sylvius (Cerebral aqueduct), fourth ventricle,foramen of Magendie (Median aperture) and foramina of Luschka(Lateral apertures), subarachnoid space over brain and spinal cord. Itshould be noted that the CSF moves in a pulsatile manner throughoutthe CSF system with nearly zero net flow. CSF is reabsorbed intovenous sinus blood via arachnoid granulations.

It had been thought that CSF returns to the vascular system by enteringthe dural venous sinuses via the arachnoid granulations (or villi).However, some have suggested that CSF flow along the cranial nervesand spinal nerve roots allow it into the lymphatic channels; this flow may play a substantial role in CSF reabsorbtion,in particular in the neonate, in which arachnoid granulations are sparsely distributed. The flow of CSF to the nasalsubmucosal lymphatic channels through the cribriform plate seems to be especially important.

Amount and constitution

Intracranial volumetric distribution ofcerebrospinal fluid, blood, and brain parenchyma

The CSF contains approximately 0.3% plasma proteins, orapproximately 15 to 40mg/dL, depending on sampling site, and it isproduced at a rate of 500 ml/day. Since the subarachnoid space aroundthe brain and spinal cord can contain only 135 to 150 ml, largeamounts are drained primarily into the blood through arachnoidgranulations in the superior sagittal sinus. Thus the CSF turns overabout 3.7 times a day. This continuous flow into the venous systemdilutes the concentration of larger, lipid-insoluble moleculespenetrating the brain and CSF.


Volumetric distribution of cerebrospinal fluid

CSF pressure, as measured by lumbar puncture (LP), is 10-18 cmH2O(8-15 mmHg or 1.1-2 kPa) with the patient lying on the side and20-30cmH2O (16-24 mmHg or 2.1-3.2 kPa) with the patient sittingup.[2] In newborns, CSF pressure ranges from 8 to 10 cmH2O(4.47.3mmHg or 0.780.98kPa). Most variations are due tocoughing or internal compression of jugular veins in the neck. Whenlying down, the cerebrospinal fluid as estimated by lumbar puncture is similar to the intracranial pressure.

There are quantitative differences in the distributions of a number of proteins in the CSF. In general, globularproteins and albumin are in lower concentration in ventricular CSF compared to lumbar or cisternal fluid. The IgGindex of cerebrospinal fluid is a measure of the immunoglobulin G content, and is elevated in multiple sclerosis. It isdefined as IgG index = (IgGCSF / IgGserum ) / (albuminCSF / albuminserum). A cutoff value has been suggested to be0.73, with a higher value indicating presence of multiple sclerosis.

Reference ranges

Reference ranges for ions and metals in CSF

Substance Lower limit Upper limit Unit Corresponds to % of that in plasmaWikipedia:Please clarify

Osmolality 280[3] 300 mmol/L

Sodium 135 150 mmol/L

Potassium 2.6 3.0 mmol/L

Chloride 115 130 mmol/L >100%

Calcium 1.00 1.40 mmol/L ~50%

Magnesium 1.2 1.5 mmol/L >100%

Iron 0.2 0.4 mol/L

Reference ranges for other molecules in CSF

Substance Lower limit Upper limit Unit Corresponds to % of that in plasma

Glucose 50[4] 80 mg/dL ~60%

2.2,[5] 2.8 3.9, 4.4 mmol/L

Protein 15 40, 45 mg/dL ~1%

Albumin 7.8[6] 40 mg/dL 0[7] - 0.7%- corresponding to an albumin (CSF/serum) quotient of 0 to 7x103

Lactate 1.1 2.4 mmol/L

Creatinine 50 110 mol/L

Phosphorus 0.4 0.6 mol/L

Urea 3.0 6.5 mmol/L

Carbon dioxide 20 25 mmol/L


Reference ranges for other CSF constituents

Substance Lower limit Upper limit Unit Corresponds to % of that in blood plasma

RBCs n/a 0 / negative cells/Lorcells/mm3

WBCs 0 3 cells/Lcells/mm3

pH 7.28 7.32 (-log M)

PCO2 44 50 mmHg

5.9[8] 6.7 kPa

PO2 40 44 mmHg

5.3 5.9 kPa

Pathology and laboratory diagnosis

Cerebrospinal fluid (CSF) at glance.

When CSF pressure is elevated, cerebral blood flow may beconstricted. When disorders of CSF flow occur, they may thereforeaffect not only CSF movement but also craniospinal compliance andthe intracranial blood flow, with subsequent neuronal and glialvulnerabilities. The venous system is also important in this equation.Infants and patients shunted as small children may have particularlyunexpected relationships between pressure and ventricular size,possibly due in part to venous pressure dynamics. This may havesignificant treatment implications, but the underlying pathophysiologyneeds to be further explored.

CSF connections with the lymphatic system have been demonstrated inseveral mammalian systems. Preliminary data suggest that theseCSF-lymph connections form around the time that the CSF secretorycapacity of the choroid plexus is developing (in utero). There may besome relationship between CSF disorders, including hydrocephalusand impaired CSF lymphatic transport.

CSF can be tested for the diagnosis of a variety of neurological diseases. It is usually obtained by a procedure calledlumbar puncture. Removal of CSF during lumbar puncture can cause a severe headache after the fluid is removed,because the brain hangs on the vessels and nerve roots, and traction on them stimulates pain fibers. This pain can berelieved by intrathecal injection of sterile isotonic saline. Lumbar puncture is performed in an attempt to count thecells in the fluid and to detect the levels of protein and glucose. These parameters alone may be extremely beneficialin the diagnosis of subarachnoid hemorrhage and central nervous system infections (such as meningitis). Moreover, aCSF culture examination may yield the microorganism that has caused the infection. By using more sophisticatedmethods, such as the detection of the oligoclonal bands, an ongoing inflammatory condition (for example, multiplesclerosis) can be recognized. A beta-2 transferrin assay is highly specific and sensitive for the detection for, e.g.,CSF leakage.


Cause Appearance PolymorphonuclearLeukocytes

Lymphocytes Protein Glucose

Pyogenic bacterialmeningitis

Yellowish, turbid Markedly increased Slightly increased orNormal

Markedly increased Decreased

Viral meningitis Clear fluid Slightly increased or Normal Markedly increased Slightly increased orNormal

Normal

Tuberculous meningitis Yellowish andviscous

Slightly increased or Normal Markedly increased Increased Decreased

Fungal meningitis Yellowish andviscous

Slightly increased or Normal Markedly increased Slightly increased orNormal

Normal ordecreased

Lumbar punctureLumbar puncture can also be performed to measure the intracranial pressure, which might be increased in certaintypes of hydrocephalus. However a lumbar puncture should never be performed if increased intracranial pressure issuspected because it can lead to brain herniation and ultimately death.

BaricityThis fluid has an importance in anesthesiology. Baricity refers to the density of a substance compared to the densityof human cerebrospinal fluid. Baricity is used in anesthesia to determine the manner in which a particular drug willspread in the intrathecal space.

Alzheimer's diseaseA 2010 study showed analysis of CSF for three protein biomarkers can indicate the presence of Alzheimer's disease.The three biomarkers are CSF amyloid beta 1-42, total CSF tau protein and P-Tau181P. In the study, the biomarkertest showed good sensitivity, identifying 90% of persons with Alzheimer's disease, but poor specificity, as 36% ofcontrol subjects were positive for the biomarkers. The researchers suggested the low specificity may be explained bydeveloping but not yet symptomatic disease in controls.

References[1] Allan H. Ropper, Robert H. Brown Adams and Victor's Principles of Neurology McGraw-Hill Professional; 8 edition (March 29, 2005) Ch.

30 p. 530.[2] THE NORMAL CSF (http:/ / neuropathology-web. org/ chapter14/ chapter14CSF. html) from Chapter Fourteen - Cerebrospinal Fluid.

Neuropathology. By Dimitri Agamanolis, Northeast Ohio Medical University . Updated: May, 2011[3] PATHOLOGY 425 CEREBROSPINAL FLUID UNIQ-nowiki-0-6ab6bb68352903f9-QINU CSF UNIQ-nowiki-1-6ab6bb68352903f9-QINU

(http:/ / www. pathology. ubc. ca/ path425/ SystemicPathology/ Neuropathology/ CerebrospinalFluidCSFDrGPBondy. rtf) at the Departmentof Pathology and Laboratory Medicine at the University of British Columbia. By Dr. G.P. Bondy. Retrieved November 2011

[4] Normal Reference Range Table (http:/ / pathcuric1. swmed. edu/ PathDemo/ nrrt. htm) from The University of Texas Southwestern MedicalCenter at Dallas. Used in Interactive Case Study Companion to Pathologic basis of disease.

[5] Department of Chemical Pathology at the Chinese University of Hong Kong (http:/ / www. cpy. cuhk. edu. hk/ wardmanual/ Menu/ DP/Glucose. htm), in turn citing: Roberts WL et al. Reference Information for the Clinical Laboratory. In Tietz Textbook of Clinical Chemistryand Molecular Diagnostics, 4th edn. Burtis CA, Ashwood ER and Bruns DE eds. Elsevier Saunders 2006; 2251 - 2318

[6] Lab Manual for SFGH > PROTEIN, CSF - IgG INDEX (http:/ / labmed. ucsf. edu/ sfghlab/ data/ tests/ 232. html) at The University ofCalifornia, San Francisco. Last updated 10/4/2010.

[7] Standardization of procedures and methods in neuroimmunology (http:/ / www. aini. it/ files/ pdf/ 48094. pdf) from the Italian Association ofNeuroimmunology. Retrieved January, 2012

[8][8] Derived from mmHg values using 0.133322 kPa/mmHg


External links Circulation of Cerebrospinal Fluid (CSF) (http:/ / www. aboutkidshealth. ca/ En/ HowTheBodyWorks/

IntroductiontotheBrain/ WhatisCerebrospinalFluidCSF/ Pages/ CirculationofCerebrospinalFluidCSF. aspx) -Interactive Tool

Cerebrospinal fluid (http:/ / neuropathology-web. org/ chapter14/ chapter14CSF. html)

Article Sources and Contributors 7

Article Sources and ContributorsCerebrospinal fluid Source: http://en.wikipedia.org/w/index.php?oldid=580157125 Contributors: 63.86.107.xxx, Ace111, Aceofhearts1968, Amaher, Amkilpatrick, Andrewpmk, Anrnusna,Antifumo, Apers0n, Arc de Ciel, Arcadian, Balul9, Basket of Puppies, Bissinger, Bobo192, Bryan Derksen, CDN99, Cai, Cerejota, Cezarika1, Chidicon, Cmcnicoll, Conversion script, Cool faces,CorporalW, Davv321, Diptanshu.D, Dlohcierekim, Dnwq, DocWatson42, Dr. St-Amant, DragonflySixtyseven, Drphilharmonic, Edgar181, Emperorbma, Eras-mus, ErdemTuzun, Erier2003,Fadliabdullah, Fantumphool, Gadlen, Gaius Cornelius, Giancarlo Rossi, Gilliam, Ginkgo100, Gouerouz, Graham87, Gromlakh, Hazard-SJ, Hede2000, Herbythyme, I dream of horses, Immunize,Inferior Olive, Irutavias, JackWasey, JakobSteenberg, Jauhienij, Jcoakes9, Jeffq, JeremyA, Jfdwolff, Jimp, Jlmoltzen, Jmacaulay, Jmh649, Joehall45, Kenn03, Kosigrim, Kruosio, Lb.at.wiki,Lipothymia, Looie496, Lova Falk, Luke poa, Mav, Maxxicum, Merenta, Mesoderm, Mikael Hggstrm, Moltovivace, N5iln, NPalmius, Nassim Abi Chahine, Nbauman, Neutrality, Nevit,NickCT, Nickkid5, Nicksh, Nivekian, Nohomers48, Nono64, NotWith, Nunh-huh, Nyttend, OohBunnies!, Pbird08, Perfect Purple Pyramid, Perfectapproach, Permacultura, PrestonH, Quarl,Qwertzy, R107, RLeopard, Rashka00, Reza luke, Rjlabs, Rjwilmsi, Rockithegreat, Rolandchee, Romanm, S7evyn, Saariko, Sbmehta, Shameerbabu986, Sjschen, Smjg, Spitfire, Srikeit,Super48paul, Tarotcards, Tarsaucer, Teacherjess2, TestSubject528491, The Thing That Should Not Be, Theolyons, Timwi, Tobias Hoevekamp, Tomaxer, Tri6ky, TurtleShroom, Ugur Basak,UseTheCommandLine, Utku Tanrivere, Vartan Balian, Vojtech.dostal, Wdustbuster, Webclient101, WereSpielChequers, White Trillium, Whiteknight, Wisdom89, WolfmanSF, Woohookitty,Wouterhagens, Wouterstomp, Wyvyrn, Ytsmith2, Zeus1234, Ziphon, 225 anonymous edits

Image Sources, Licenses and ContributorsImage:4 vials of human cerebrospinal fluid.jpg Source: http://en.wikipedia.org/w/index.php?title=File:4_vials_of_human_cerebrospinal_fluid.jpg License: Creative Commons Attribution 3.0Contributors: James Heilman, MDFile:NPH MRI 272 GILD.gif Source: http://en.wikipedia.org/w/index.php?title=File:NPH_MRI_272_GILD.gif License: unknown Contributors: Nevit Dilmen (talk)File:dist csf.png Source: http://en.wikipedia.org/w/index.php?title=File:Dist_csf.png License: Creative Commons Zero Contributors: Tarsaucer (talk)File:dist vent.png Source: http://en.wikipedia.org/w/index.php?title=File:Dist_vent.png License: Creative Commons Zero Contributors: User:SreeBot, User:TarsaucerImage:CSFposter1p.png Source: http://en.wikipedia.org/w/index.php?title=File:CSFposter1p.png License: Public domain Contributors: JackWasey

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Cerebrospinal fluidFunctionsHistoryCirculationAmount and constitutionReference ranges

Pathology and laboratory diagnosisLumbar punctureBaricityAlzheimer's diseaseReferences External links

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Cerebrospinal Fluid