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Cerebrospinal fluid and its physiology
PHYSIOLOGY
Cerebrospinal fluid and its physiology
Learning objectives After reading this article, you should be able to: C outline the anatomy of the production pathways CSF C explain the functions of CSF C describe the production, flow and absorption of CSF and how abnormalities of these pathways can result in hydrocephalus
Rosie May Ugan Reddy
Abstract This article describes the anatomy and physiology of CSF, and how abnormalities can result in hydrocephalus.
CSF production, flow and reabsorption CSF is predominantly produced in the choroid plexus of the lateral, third and fourth cerebral ventricles through the processes of filtration and secretion. It is produced at a rate of around 0.3 ml/minute, resulting in 400e600 ml secretion per day. The total circulating volume in the ventricles and subarachnoid spaces is roughly 150 ml, around two-thirds of which is intracranial, and the other third spinal. The choroid plexus is a core of fenestrated capillaries lined with a single layer of epithelial cells. Water and solutes are filtered from the plasma within the choroidal capillaries into the epithelial cells. This process is dependent on an adequate cerebral perfusion pressure, creating a pressure gradient across the choroidal capillaries. This is followed by secretion through active transport of solutes across the epithelium into the ventricular lumen. The latter process is tightly controlled by the autonomic nervous system and ligands such as dopamine, serotonin and vasopressin. A small proportion of CSF is produced extrachoroidally, via secretion from extracellular fluid and cerebral capillaries. CSF flow is pulsatile and oscillates in phase with the choroidal blood flow. It flows from sites of production to absorption in a rostrocaudal direction within the ventricles, and a multidirectional manner within the subarachnoid spaces, aided by ciliary movements of ependymal cells. CSF secreted into the lateral ventricles circulates to the third ventricle through the foramen of Monro, and then to the fourth ventricle through the cerebral aqueduct. It leaves the fourth ventricle through the foramen of Magendie, which lies in the midline posteriorly, and the foramen of Luschka, which lie laterally, and subsequently passes into the subarachnoid spaces of the spinal cord and the cerebral hemispheres. A small amount of CSF flows through the central canal of the spinal cord (Figure 1). CSF is reabsorbed via arachnoid villi and granulations into the dural venous sinuses, as well as through cranial and spinal nerve sheaths into the lymphatic outflow system. Arachnoid villi are small endothelium lined projections of arachnoid mater, which invaginate through the dura mater into the lumen of the venous sinuses. Reabsorption is dependent on a pressure gradient existing across the arachnoid granulations; the higher the intracranial pressure, the higher the rate of reabsorption. This is a one-way system, however, and flow cannot be reversed in case of raised venous pressure.
Keywords Cerebral ventricles; cerebrospinal fluid; choroid plexus; hydrocephalus Royal College of Anaesthetists CPD matrix: 1A01
Introduction Cerebrospinal fluid (CSF) is an ultrafiltrate of plasma that is contained within the subarachnoid spaces of the brain and spinal cord and in the ventricular system. Its main functions are to protect the neural structures that it surrounds as well as providing nutrients and removing waste products of central nervous system metabolism. Abnormalities in production, flow and absorption of CSF can all result in hydrocephalus.
CSF function CSF provides hydromechanical protection of the brain and spinal cord through buoyancy. This occurs due to the low specific gravity of CSF which reduces the effective weight of the brain to around 50 g, reducing inertia and protecting the neural structures from acceleration and deceleration forces as result. It also has an important metabolic role in maintaining homeostasis of the interstitial fluid of the brain parenchyma, as well as providing a constant source of nutrients for the regulation of neuronal functioning, and removal of waste products of neuronal metabolism. Micronutrients that are not able to diffuse through the bloodebrain barrier but are required for neuronal cell metabolism (e.g. folate and vitamin C) are actively secreted into the CSF, as are a number of hormones such a thyroid hormones. CSF plays an important role in the control of respiration, as it has a reduced acid-base buffering capacity when compared with blood. As such, small changes in PCO2 cause relatively large fluctuations in pH and resultant activation of central chemoreceptors.
Rosie May MBBS MA(Cantab) MRCP FRCA is a Fellow in Neuroanaesthesia and Neurocritical care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared. Ugan Reddy BSc MBChB FRCA FFICM is Director of the Surgical Intensive Therapy Unit and Consultant in Neuroanaesthesia and Neurocritical Care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
CSF composition The bloodebrain barrier separates the CSF from the plasma, allowing a concentration difference to exist between the
1
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: May R, Reddy U, Cerebrospinal fluid and its physiology, Anaesthesia and intensive care medicine, https://doi.org/ 10.1016/j.mpaic.2019.10.017
PHYSIOLOGY
Causes of hydrocephalus
Lateral view of ventricles Arachnoid granulations
Subarachnoid space containing CSF
Superior sagittal sinus
Choroid plexus
Lateral ventricles
Mechanism
Pathology
Overproduction of CSF Obstruction of CSF flow Foramen of Monro Cerebral aqueduct Outlets of fourth ventricle
Choroid plexus papilloma
Basal cisterns
Tumour, congenital abnormality Tumour, congenital abnormality Chronic meningitis, Chiari malformation Meningitis, post-subarachnoid haemorrhage
Decreased CSF absorption Arachnoid granulation damage Haemorrhage, meningitis Increased cerebral venous pressure Skull base anomalies, internal jugular vein thrombosis, congenital heart disease
Foramen of Monro
Table 2
Third ventricle
Fourth ventricle
Lateral apertures
CSF pressure
Cisterna magna
Cerebral aqueduct
CSF pressure is defined as the intracranial pressure (ICP) in the horizontal position and this is normally 10e15 mmHg in an adult, and 3e4 mmHg in infants. There is a normal physiological variation in this pressure with posture, respiratory and cardiac cycles, changes in arterial and venous pressure and cerebral activity. This is usually compensated for by changes in CSF or blood volume, as described by the MonroKellie doctrine; the cranial cavity is a rigid, closed container, thus any change in intracranial blood volume is accompanied by the opposite change in CSF volume if ICP is maintained. Over-production, obstruction to flow and reduced reabsorption of CSF can all result in abnormally increased intracranial pressure, and when this pressure is sustained it can overwhelm the brains compensatory mechanisms and result in hydrocephalus (Table 2). Conversely, reduced production or over drainage can lead to intracranial hypotension. Hydrocephalus can be classified as communicating or noncommunicating. Non-communicating hydrocephalus is also known as obstructive hydrocephalus and results when there is an obstruction to CSF flow within the ventricular system. In communicating hydrocephalus, there is free flow of CSF between the ventricles and subarachnoid spaces. A
Median aperture
Arrows show direction of circulation of CSF
Central canal (of spinal cord)
Figure 1
Composition of normal plasma and CSF Solute
Plasma
CSF
Sodium Potassium Calcium Magnesium Chloride Bicarbonate Glucose Total protein
138 mmol le1 4.5 mmol le1 2.4 mmol le1 1.7 mmol le1 102 mmol le1 24 mmol le1 5.0 mmol le1 70 g le1
138 mmol le1 2.8 mmol le1 1.1 mmol le1 0.3 mmol le1 119 mmol le1 22 mmol le1 3.3 mmol le1 0.35 g le1
Table 1
composition of the two fluids (Table 1). CSF concentrations of sodium, chloride and magnesium Ions are higher than plasma, whereas those of potassium and calcium are lower. There is significantly less protein in the CSF, resulting in a limited capacity for acid-base buffering.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
FURTHER READING Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. European Annals of Otorhinolaryngology, Head and neck diseases 2011; 128: 309e16.
2
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: May R, Reddy U, Cerebrospinal fluid and its physiology, Anaesthesia and intensive care medicine, https://doi.org/ 10.1016/j.mpaic.2019.10.017
Cerebrospinal fluid and its physiology
Learning objectives After reading this article, you should be able to: C outline the anatomy of the production pathways CSF C explain the functions of CSF C describe the production, flow and absorption of CSF and how abnormalities of these pathways can result in hydrocephalus
Rosie May Ugan Reddy
Abstract This article describes the anatomy and physiology of CSF, and how abnormalities can result in hydrocephalus.
CSF production, flow and reabsorption CSF is predominantly produced in the choroid plexus of the lateral, third and fourth cerebral ventricles through the processes of filtration and secretion. It is produced at a rate of around 0.3 ml/minute, resulting in 400e600 ml secretion per day. The total circulating volume in the ventricles and subarachnoid spaces is roughly 150 ml, around two-thirds of which is intracranial, and the other third spinal. The choroid plexus is a core of fenestrated capillaries lined with a single layer of epithelial cells. Water and solutes are filtered from the plasma within the choroidal capillaries into the epithelial cells. This process is dependent on an adequate cerebral perfusion pressure, creating a pressure gradient across the choroidal capillaries. This is followed by secretion through active transport of solutes across the epithelium into the ventricular lumen. The latter process is tightly controlled by the autonomic nervous system and ligands such as dopamine, serotonin and vasopressin. A small proportion of CSF is produced extrachoroidally, via secretion from extracellular fluid and cerebral capillaries. CSF flow is pulsatile and oscillates in phase with the choroidal blood flow. It flows from sites of production to absorption in a rostrocaudal direction within the ventricles, and a multidirectional manner within the subarachnoid spaces, aided by ciliary movements of ependymal cells. CSF secreted into the lateral ventricles circulates to the third ventricle through the foramen of Monro, and then to the fourth ventricle through the cerebral aqueduct. It leaves the fourth ventricle through the foramen of Magendie, which lies in the midline posteriorly, and the foramen of Luschka, which lie laterally, and subsequently passes into the subarachnoid spaces of the spinal cord and the cerebral hemispheres. A small amount of CSF flows through the central canal of the spinal cord (Figure 1). CSF is reabsorbed via arachnoid villi and granulations into the dural venous sinuses, as well as through cranial and spinal nerve sheaths into the lymphatic outflow system. Arachnoid villi are small endothelium lined projections of arachnoid mater, which invaginate through the dura mater into the lumen of the venous sinuses. Reabsorption is dependent on a pressure gradient existing across the arachnoid granulations; the higher the intracranial pressure, the higher the rate of reabsorption. This is a one-way system, however, and flow cannot be reversed in case of raised venous pressure.
Keywords Cerebral ventricles; cerebrospinal fluid; choroid plexus; hydrocephalus Royal College of Anaesthetists CPD matrix: 1A01
Introduction Cerebrospinal fluid (CSF) is an ultrafiltrate of plasma that is contained within the subarachnoid spaces of the brain and spinal cord and in the ventricular system. Its main functions are to protect the neural structures that it surrounds as well as providing nutrients and removing waste products of central nervous system metabolism. Abnormalities in production, flow and absorption of CSF can all result in hydrocephalus.
CSF function CSF provides hydromechanical protection of the brain and spinal cord through buoyancy. This occurs due to the low specific gravity of CSF which reduces the effective weight of the brain to around 50 g, reducing inertia and protecting the neural structures from acceleration and deceleration forces as result. It also has an important metabolic role in maintaining homeostasis of the interstitial fluid of the brain parenchyma, as well as providing a constant source of nutrients for the regulation of neuronal functioning, and removal of waste products of neuronal metabolism. Micronutrients that are not able to diffuse through the bloodebrain barrier but are required for neuronal cell metabolism (e.g. folate and vitamin C) are actively secreted into the CSF, as are a number of hormones such a thyroid hormones. CSF plays an important role in the control of respiration, as it has a reduced acid-base buffering capacity when compared with blood. As such, small changes in PCO2 cause relatively large fluctuations in pH and resultant activation of central chemoreceptors.
Rosie May MBBS MA(Cantab) MRCP FRCA is a Fellow in Neuroanaesthesia and Neurocritical care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared. Ugan Reddy BSc MBChB FRCA FFICM is Director of the Surgical Intensive Therapy Unit and Consultant in Neuroanaesthesia and Neurocritical Care at the National Hospital for Neurology and Neurosurgery, London, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
CSF composition The bloodebrain barrier separates the CSF from the plasma, allowing a concentration difference to exist between the
1
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: May R, Reddy U, Cerebrospinal fluid and its physiology, Anaesthesia and intensive care medicine, https://doi.org/ 10.1016/j.mpaic.2019.10.017
PHYSIOLOGY
Causes of hydrocephalus
Lateral view of ventricles Arachnoid granulations
Subarachnoid space containing CSF
Superior sagittal sinus
Choroid plexus
Lateral ventricles
Mechanism
Pathology
Overproduction of CSF Obstruction of CSF flow Foramen of Monro Cerebral aqueduct Outlets of fourth ventricle
Choroid plexus papilloma
Basal cisterns
Tumour, congenital abnormality Tumour, congenital abnormality Chronic meningitis, Chiari malformation Meningitis, post-subarachnoid haemorrhage
Decreased CSF absorption Arachnoid granulation damage Haemorrhage, meningitis Increased cerebral venous pressure Skull base anomalies, internal jugular vein thrombosis, congenital heart disease
Foramen of Monro
Table 2
Third ventricle
Fourth ventricle
Lateral apertures
CSF pressure
Cisterna magna
Cerebral aqueduct
CSF pressure is defined as the intracranial pressure (ICP) in the horizontal position and this is normally 10e15 mmHg in an adult, and 3e4 mmHg in infants. There is a normal physiological variation in this pressure with posture, respiratory and cardiac cycles, changes in arterial and venous pressure and cerebral activity. This is usually compensated for by changes in CSF or blood volume, as described by the MonroKellie doctrine; the cranial cavity is a rigid, closed container, thus any change in intracranial blood volume is accompanied by the opposite change in CSF volume if ICP is maintained. Over-production, obstruction to flow and reduced reabsorption of CSF can all result in abnormally increased intracranial pressure, and when this pressure is sustained it can overwhelm the brains compensatory mechanisms and result in hydrocephalus (Table 2). Conversely, reduced production or over drainage can lead to intracranial hypotension. Hydrocephalus can be classified as communicating or noncommunicating. Non-communicating hydrocephalus is also known as obstructive hydrocephalus and results when there is an obstruction to CSF flow within the ventricular system. In communicating hydrocephalus, there is free flow of CSF between the ventricles and subarachnoid spaces. A
Median aperture
Arrows show direction of circulation of CSF
Central canal (of spinal cord)
Figure 1
Composition of normal plasma and CSF Solute
Plasma
CSF
Sodium Potassium Calcium Magnesium Chloride Bicarbonate Glucose Total protein
138 mmol le1 4.5 mmol le1 2.4 mmol le1 1.7 mmol le1 102 mmol le1 24 mmol le1 5.0 mmol le1 70 g le1
138 mmol le1 2.8 mmol le1 1.1 mmol le1 0.3 mmol le1 119 mmol le1 22 mmol le1 3.3 mmol le1 0.35 g le1
Table 1
composition of the two fluids (Table 1). CSF concentrations of sodium, chloride and magnesium Ions are higher than plasma, whereas those of potassium and calcium are lower. There is significantly less protein in the CSF, resulting in a limited capacity for acid-base buffering.
ANAESTHESIA AND INTENSIVE CARE MEDICINE xxx:xxx
FURTHER READING Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. European Annals of Otorhinolaryngology, Head and neck diseases 2011; 128: 309e16.
2
Ó 2019 Published by Elsevier Ltd.
Please cite this article as: May R, Reddy U, Cerebrospinal fluid and its physiology, Anaesthesia and intensive care medicine, https://doi.org/ 10.1016/j.mpaic.2019.10.017