Physiology, Cerebral Spinal Fluid (CSF)


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Lauren Telano


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Updated:
10/27/2018 12:32:09 PM

Introduction

Cerebrospinal fluid (CSF) is an ultrafiltrate of plasma contained within the ventricles of the brain and the subarachnoid spaces of the cranium and spine.[1] It performs vital functions including providing nourishment, waste removal, and protection to the brain.[2] Adult CSF volume is estimated to be 150 ml with a distribution of 125 ml within the subarachnoid spaces and 25 ml within the ventricles. CSF is predominantly secreted by the choroid plexus with other sources playing a more poorly defined role. Its secretion varies between individuals with adult production, usually ranging between 400 to 600 ml per day. The constant secretion of CSF contributes to complete CSF renewal four to five times per 24-hour period in the average young adult. Reduction of CSF turnover may contribute to the accumulation of metabolites seen in aging and neurodegenerative diseases. The composition of CSF is closely regulated, and any variation can be used for diagnostic purposes.[1]

Cellular

Seventy to eighty percent of CSF is produced via a network of modified ependymal cells known as the choroid plexus (CP).[1] The CP is a highly specialized simple cuboidal epithelium continuous with ependymal cells lining the ventricles of the brain. This simple cuboidal epithelium surrounds clusters of fenestrated capillaries allowing for the filtration of plasm[3] Cells of the CP have dense microvilli present on their apical surface and are interconnected via tight junctions, creating a blood-CSF barrier that helps to control the composition of CSF.[1] Because there is no appreciable barrier between the CSF and the extracellular space of the brain (ECSB), the blood-CSF barrier also serves to regulate the environment of the brain.[2] Larger substances such as cells, protein, and glucose are not allowed passage whereas ions and small molecules such as vitamins and nutrients are able to pass into the CSF relatively easily.[4] Water is allowed passage through the CP epithelium via epithelial AQP1 channels. Substances that may not pass through the blood-CSF barrier but are needed by the brain can be actively synthesized by or actively transported through the CP epithelial cells into the CSF. A 5 mV lumen positive voltage potential is present across CP epithelial cell membranes. This difference of electrical potential pulls sodium, chloride, and bicarbonate ions from the plasma into the CSF, creating an osmotic gradient which then drives the movement of water into the CSF.[3] When compared to plasma, CSF has a higher concentration of sodium, chloride, and magnesium but a lower concentration of potassium and calcium.[1] Unlike plasma, CSF has only trace amounts of cells, protein, and immunoglobulins.[2] No cells are able to pass through the blood-CSF barrier although small numbers of white blood cells are usually introduced to the CSF indirectly. Normal cell count of CSF is usually lower than 5 cells/ml.[1] Despite changes in blood composition and flow, the composition of CSF is kept constant. This provides a stable intraventricular environment, critical for maintaining normal neuronal function.[3]

Function

CSF assists the brain by providing protection, nourishment, and waste removal.[2] CSF provides hydromechanical protection of the neuraxis through two mechanisms.[1] First, CSF acts as a shock absorber, cushioning the brain against the skull. Second, CSF allows the brain and spinal cord to become buoyant, reducing the effective weight of the brain from its normal 1,500 grams to a much lesser 50 grams. The reduction in weight lessens the force applied to the brain parenchyma and cerebral vessels during mechanical injury.[3] Another function of CSF is to maintain homeostasis of the interstitial fluid of the brain. A stable environment for brain parenchyma is imperative for maintaining normal neuronal function.[1] The major conduit of nutrient supply to the brain is the CP-CSF-ECSB nexus. Substrates needed by the brain are transported from the blood, through the CP, into the CSF, and then diffuse into the ECSB for transportation to their sites of action within the brain.[2] CSF also assists in the removal of waste products of brain metabolism, such as products of peroxidation, glycosylated proteins, excess neurotransmitters, debris from the lining of the ventricles, bacteria, viruses, and otherwise unnecessary molecules.[2][1][3] Accumulation of such unnecessary molecules, seen in aging and some neurodegenerative diseases, interferes with neuronal functioning of the brain. The great importance of CSF functioning is suggested by disruption of cerebral physiology experienced when the hydrodynamics or composition of CSF is disrupte[1]  

Mechanism

CSF is secreted constantly with an unchanging composition, functioning to maintain a stable environment within the brain.[3] CSF is propelled along the neuroaxis from the site of secretion to the site of absorption mainly by the rhythmic systolic pulse wave within the choroidal arteries. Lesser determinants of CSF flow are frequency of respiration, posture, venous pressure of the jugular vein, physical effort of the subject, and time of day.[2]

CSF is secreted by the CPs located within the ventricles of the brain, with the two lateral ventricles being the primary producers. CSF flows throughout the ventricular system unidirectionally in a rostral to caudal manner. CSF produced in the lateral ventricles would travel through the interventricular foramina to the third ventricle, through the cerebral aqueduct to the fourth ventricle, and then through the median aperture (also known as the foramen of Magendie) into the subarachnoid space at the base of the brai[1]  Once in the subarachnoid space, the CSF begins have a gentle multidirectional flow that creates an equalization of composition throughout the CS[2] CSF flows over the surface of the brain and down the length of spinal cord while in the subarachnoid space. It leaves the subarachnoid space through arachnoid villi found along the superior sagittal venous sinus, intracranial venous sinuses, and around the roots of spinal nerves. Arachnoid villi are protrusions of arachnoid mater through the dura mater into the lumen of a venous sinus.  A 3 to 5 mmHg pressure gradient between the subarachnoid space and venous sinus pulls CSF into the venous outflow system through the arachnoid villi which act [1] CSF may also enter into the lymphatic system via the nasal cribriform plate or spinal nerve roots. Clearance of CSF is dependent upon the posture of the subject, pressure differentials, and pathophysiology.[2]

Related Testing

Lumbar puncture (LP), also known as spinal tap, is a commonly performed invasive procedure in which CSF is removed from the subarachnoid space. LP is used in the measurement of intracranial pressure and the sampling of CSF. It is commonly indicated in the evaluation of acute headache and infection of the central nervous system.[5] During a LP the patient is placed in the lateral recumbent position. A sterile spinal needle is then slowly inserted between vertebrae, usually at the level of L3/4 or L4/5, into the subarachnoid space.[6] Needle insertion may be guided by fluoroscopy or ultrasound in order to improve success rates and reduce the incidence of trauma.[5] Once CSF begins to flow through the needle, it is collected serially into four sterile tubes. Once collected, CSF can be analyzed for abnormally present or elevated CSF components, aiding in diagnosis. For example, the presence of xanthochromia, a yellow-orange discoloration of CSF caused by red blood cell degeneration, indicates the possibility of a subarachnoid hemorrhage. Elevation in concentrations of immunoglobulins, termed oligoclonal bands, may indicate the presence of a systemic infection or an autoimmune disease. Contraindications of LP include raised intracranial pressure, bleeding disorders, and local skin infection.[6] This procedure is relatively safe with serious complications seldomly arising.[5] Complications of LP include: infection, bleeding, radicular pain, or cerebral herniation.[6] The most common complication is a post-LP headache with symptoms begin within 24 hours of the procedure and usually resolving by day 10.[5]  

Clinical Significance

Hydrocephalus is a pathological condition of abnormal accumulation of CSF caused by increased CSF production, blockage of flow, or decreased absorption. The ventricles distend in order to accommodate elevated CSF volumes, potentially causing damage to the brain by pressing its tissue against the boney skull. Hydrocephalus may be congenital or acquired.[7] If the flow of CSF is blocked throughout the ventricles, it is classified as non-communicating, or obstructive, hydrocephalus.[8] Usually the blockage is a mass such as a tumor or abscess located within a foramen. Because CSF is constantly secreted, an obstruction of flow will lead to CSF build up in front of the blockage.[7] For example, stenosis of the cerebral aqueduct, one of the most common causes of obstructive hydrocephalus, leads to enlargement of both lateral ventricles as well as the third ventricle. If the flow of CSF is obstructed outside the ventricles, in either the subarachnoid space or site of absorption, it is classified as communicating, or non-obstructive, hydrocephalus.[8] Hydrocephalus can be caused by genetic defects, infection, bleeding in the brain, trauma, or CNS tumors.[7] Symptoms include headache, convulsions, nausea, vomiting, disturbances of vision, and mental deterioration.[7][7] Diagnosis is usually achieved through the use of imaging techniques such as ultrasound, CT, or MR[8] The most common treatment is insertion of a shunt which diverts CSF away from the ventricles to an area of the body where is can be absorbed into circulation.[7] Endoscopic third ventriculostomy, a procedure in which a hole is created in the floor of the third ventricle allowing CSF to bypass obstruction, and cauterization of sections of CP, decreasing CSF production, are other treatment options.  If left untreated, hydrocephalus yields a risk of cognitive disturbances, physical disturbances, and death.[8]

CSF Leak is a condition in which CSF is able escape from the subarachnoid space through a hole in the surrounding dura. The volume of CSF lost in a leak is very variable, ranging from insignificant to very substantial amounts. If the loss of CSF is great enough, spontaneous intracranial hypotension (SIH) may occur. SIH most often presents with a positional headache caused by downward displacement of the brain due to loss of buoyancy previously provided by the CSF. Posterior neck stiffness, nausea, and vomiting are also common symptoms. The incidence of SIH is estimated to be 5/100,000 annually. Women are two times more likely to be affected with the peak age at around 40 years. Diagnosis is aided by typical MRI findings, such as an increase of intracranial venous volume, pituitary hyperemia, enhanced pachymeninges, and descent of the brain. Many cases of SIH resolve without any treatment. Conservative approaches such as bed rest, hydration, and increased caffeine intake may also prove to be effective; however, more drastic measures may be necessary. An epidural blood patch, where blood is injected into the spinal epidural space, may relieve CSF hypovolemic symptoms by replacing lost CSF volume with blood volume. Surgical repair of the CSF leak via a suture or metal aneurysm clip is relatively safe and usually effective in providing relief.[9]

Meningitis is a condition in which the coverings of the brain become inflamed. There are two classifications of meningitis: aseptic and bacterial. Aseptic meningitis can be caused by agents such as fungi, medications, and cancer metastasis, but the majority of aseptic meningitis cases are caused by viruses. Fever, nuchal rigidity, and photophobia are classic presenting symptoms. Diagnosis is made via an analysis of CSF obtained through LP. Viral PCR analysis of CSF is particularly helpful in diagnosing viral meningitis. Treatment is usually supportive, controlling fever and pain levels. Bacterial meningitis has a much lower incidence than aseptic meningitis but is much more serious. The incidence of bacterial meningitis has significantly dropped due to routine vaccination. Symptoms are similar to aseptic meningitis but clinical presentation is much more severe. Additional symptoms include altered mental status, seizures, and focal neurologic signs. Diagnosis is also achieved via LP. CSF is usually cloudy in appearance, with a low glucose level, and possible positive gram stain and culture. Patients presumed to have bacterial meningitis should immediately be given broad-spectrum antibiotics to prevent clinical deterioration. After culture results return, adjustments to the antibiotics can be made. Patients should also be admitted into the intensive care unit for close monitoring. Most patients with bacterial meningitis who receive appropriate treatment recover without complications.[10]

Subarachnoid Hemorrhage (SAH) is the leakage of blood into the subarachnoid space where it mixes with the CSF. SAH is most commonly caused by trauma with 80% of nontraumatic SAHs being caused by aneurysm rupture. Other nontraumatic causes of SAH include arteriovenous malformations and vasculitis. Spontaneous SAH is very low incidence with with only 30,000 cases worldwide annually. Ninety-seven percent of patients with SAH present with a sudden onset headache that is described as thunderclap and the worst of the patient's life. Other symptoms include vomiting, seizures, loss of consciousness, and death. Non-contrast head CT is used in diagnosis. CT has high sensitivity soon after hemorrhage, but sensitivity decreases as time passes. After a negative CT is obtained, a LP is recommended to adequately rule out SAH. A LP is considered positive when erythrocytes are present in tube 1 and 4 or xanthochromia is visible. Management of SAH consists of reducing risks of re-bleeding and avoiding any secondary brain injuries.[11]

Pseudotumor Cerebri Syndrome (PTCS) is a rare medical condition in which intracranial pressure is raised without occurrence of ventriculomegaly or intracranial masses. The pathogenesis is still not well understood. The most widely accepted theory proposes decreased absorption of CSF at the arachnoid granulations or the olfactory lymphatics to be the cause. This condition has an annual incidence rate of 0.9/100,000 in the general population. Before puberty, both females and males are affected the same, but after puberty, women are affected 9 times more often. PTCS most commonly affects obese women of childbearing age. Women between the ages of 20 and 44 years and weigh 20% more than their ideal body weight have an incidence rate of 19.3/100,000. A spinal fluid examination is critical in the diagnosis of PTCS. CSF pressure is greater than 250 mm CSF in adults and 280 mm CSF in children and adolescents are accepted values for diagnosis PTCS. Headache is the most common presenting symptom, though there are no specific distinguishing characteristics of a PTCS headache.  Occasionally asymptomatic patients present with papilledema detected during routine eye exams. Pulsatile tinnitus, transient visual obscurations, visual field defects, and visual loss are some other symptoms of PTCS. Traditional therapy includes medications to decrease CSF secretion from the choroid plexus. Surgery is indicated for patients experiencing worsening vision cause by papilledema. Surgical options include optic nerve sheath fenestration and CSF shunting. Most patients with PTCS experience a good outcome, although a small percentage of patients are left with persistent headaches or blindness. [12]


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Physiology, Cerebral Spinal Fluid (CSF) - Questions

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A 54-year-old woman presents to the emergency department with a headache, nausea, vomiting, and diplopia. An MRI of her head shows enlargement of both lateral ventricles as well as the third ventricle. The fourth ventricle is of normal size. The patient has obstructive hydrocephalus. Where is the blockage of cerebrospinal fluid (CSF) flow located?



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Which of the following would be able to passively enter into the cerebrospinal fluid through the choroid plexus epithelium?



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Which of the following does cerebrospinal fluid provide to the brain?



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A 49-year-old male presents to the emergency department with nausea and a diffuse headache rated a 7/10 on the pain scale. One month previous he was treated at for meningitis. An MRI shows diffuse ventricular dilation leading to the diagnosis of communicating, non-obstructive hydrocephalus. At which of the following areas could the flow of cerebrospinal fluid be impaired?



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What cell type is responsible for the production of cerebrospinal fluid?



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Physiology, Cerebral Spinal Fluid (CSF) - References

References

Spector R,Robert Snodgrass S,Johanson CE, A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans. Experimental neurology. 2015 Nov     [PubMed]
Damkier HH,Brown PD,Praetorius J, Epithelial pathways in choroid plexus electrolyte transport. Physiology (Bethesda, Md.). 2010 Aug     [PubMed]
Sakka L,Coll G,Chazal J, Anatomy and physiology of cerebrospinal fluid. European annals of otorhinolaryngology, head and neck diseases. 2011 Dec     [PubMed]
Damkier HH,Brown PD,Praetorius J, Cerebrospinal fluid secretion by the choroid plexus. Physiological reviews. 2013 Oct     [PubMed]
Doherty CM,Forbes RB, Diagnostic Lumbar Puncture. The Ulster medical journal. 2014 May     [PubMed]
Wright BL,Lai JT,Sinclair AJ, Cerebrospinal fluid and lumbar puncture: a practical review. Journal of neurology. 2012 Aug     [PubMed]
Orešković D,Klarica M, Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: facts and illusions. Progress in neurobiology. 2011 Aug     [PubMed]
Kahle KT,Kulkarni AV,Limbrick DD Jr,Warf BC, Hydrocephalus in children. Lancet (London, England). 2016 Feb 20     [PubMed]
Schievink WI, Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006 May 17     [PubMed]
Putz K,Hayani K,Zar FA, Meningitis. Primary care. 2013 Sep     [PubMed]
Abraham MK,Chang WW, Subarachnoid Hemorrhage. Emergency medicine clinics of North America. 2016 Nov     [PubMed]
Friedman DI, The pseudotumor cerebri syndrome. Neurologic clinics. 2014 May     [PubMed]

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