CSF-and-Blood-Brain-Barrier

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CSF and Blood Brain Barrier:

CSF and Blood Brain Barrier

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4 From: Laterra J et al., in Basic Neurochemistry Cerebrospinal fluid (CSF)

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Cerebro spinal fluid production & Circulation Clear, colourless , alkaline fluid is found in Ventricles of brain Cisterns around brain Subarachnoid space around brain and spinal cord

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Choroid Plexus : Temporal horn of each lateral ventricle Choroid plexus present in Posterior portion of III ventricle Roof of IV ventricle Vascular fringes of piamater break up into complex capillary network covered by cuboidal epithelial cells, Cells contain mitochondria, granules, vesicles indicating involvement in active metabolic process ( secretory )

Choroid Plexus:

Choroid Plexus 7

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Arachnoid villi Microscopic finger like projections of arachnoid membrane into walls of venous sinuses. Lined by endothelial cells Large conglomerates of villi called arachnoid granulations / pachionian bodies Electron microscopic study shows transcellular channels / pores in lining endothelium which allows free absorption of CSF, proteins.

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9

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Perivascular space : Blood vessel entering brain substance will carry with it sleeve of arachnoid immediately surrounding the vessel and sleeve of pia more externally. Extension of SAS around the vessel known as PV space / virchow robin space. Products of metabolism, inflammatory exudates pass from brain substance into perivascular space, to enter CSF in subarachnoid space. Formation of CSF Active secretion by choroid plexus Trans ependymal diffusion of brains interstitial fluid into ventricles (minimal)

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Secretion : Na + K + ATPase , carbonic anhydrase takes part in Active transport of Na+ occurs through epithelial cells lining choroid plexus Na + will carry Cl - with it. Na + & Cl - increase the quantitiy of osmoticaly active substances in CSF, which cause immediate osmosis of water through the membrane. Less important transport process move small amount of glucose into CSF, K + & HCO3- out of CSF

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13 Net transport of Na + and Cl - across the epithelium results in the secretion of CSF. Cl - efflux from the epithelium to CSF is mediated by a cotransporter. The generation of H + and HCO 3 by carbonic anhydrase is important in the secretion of CSF. From: Laterra J et al., in Basic Neurochemistry Production of CSF

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Resulting characteristics of CSF : Osmotic pressure & Na + equal to plasma Cl - 15% greater than plasma K + 40% less than plasma Glucose 30% less than plasma

CSF formation:

CSF formation 50% by choroid plexuses in the ventricles 40% by meningeal blood vessels and ependymal lining of ventricles 10% by brain and spinal cord blood vessels Absorption 80% by arachinoid villi into venous sinuses and spinal veins 20% by cervical lymphatics and perivascular spaces

CSF:

CSF CSF is a clear colorless, isotonic alkaline fluid, almost protein and cell free and contains less glucose and k+ than plasma. Volume- 130-150ml Daily secretion-500-550ml Rate of formation-0.2-0.3ml/min Pressure-130mm of water

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Circulation : From lateral ventricles through foramen of monro / inter ventricular foramen to III ventricle From III ventricle through cerebral aqueduct of sylvius to IV ventricle From IV ventricle leaves via median and lateral apertures of magendie and luschka to reach SAS covering cerebrum and spinal cord After bathing surface of spinal cord and base of brain CSF passes upward over convexity of hemispheres to be absorbed in intracranial venous sinuses.

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21

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Absorption : 4/5 th of CSF absorbed via cerebral arachnoid villi 1/5 th spinal arachnoid villi Hydrostatic pressure in sub arachnoid space is higher than in dural sinuses facilitates fluid movement Small amount pass into perivascular space, sheath of cranial nerves Characteristics of CSF pH 7.31 – 7.34 Specific gravity - 1005 Osmolarity 290 – 295 mosm /l Volume 70-120 ml (25ml ventricles 25 ml spinal theca)

Force of circulation:

Force of circulation Movement of the CSF is by pulsating blood vessels, respiration and changes of posture CSF is secreted continuously at a rate of about 0.5ml per minute i.e. 720 ml per day Total CSF in the brain 120 ml CSF pressure can be measured by attaching a vertical tube to the lumbar puncture needle – 10 cm water 25

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Rate of formation : 0.35 ml / min 500 ml / day Constituents mg / dl Plasma CSF Protein 7000-8000 20-40 Glucose 70-110 40-70 Nacl 560-630 720-750 Cholestrol 130-230 Nil Urea 20-40 10-30 Creatinine 0.6 – 1.5 0.5 – 1.9 Uric acid 2 – 8 0.5 – 2.5 Phosphates 2- 4 1.2 – 2.0

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Constituent osmol / litre Plasma CSF Na+ 136 – 145 137-145 K+ 3.5 – 5.0 2.7 – 3.9 Ca2+ 4.5 – 5.5 2.1 – 3.0 Mg 2+ 1.3 – 2.1 2.0 – 2.5 Cl- 98 – 106 116-122 HCO3- 21-27 20-24 pH units 7.36 – 7.44 7.31 – 7.34 Osmolarity 290 – 295 285-295 CSF Pressure : Lateral recumbent - 60 – 180 mm H2O Shifting - 300 mm H2O

Hydrocephalus:

Hydrocephalus Obstructive hydrocephalus Congenital malformations After inflammation or hemorrhage Mass lesions Communicating hydrocephalus Overproduction of CSF Defective absorption of CSF Venous drainage insufficiency

Normal Brain:

Normal Brain 39

Normal Ventricles:

Normal Ventricles 40

Hydrocephalus :

Hydrocephalus 41

Hydrocephalus :

Hydrocephalus 42

Normal ventricles and hydrocephalus:

Normal ventricles and hydrocephalus 43

Cerebral Edema:

Cerebral Edema Vasogenic edema: A state of increased extracellular fluid volume; Brain tumor, abscess, infarct, hemorrhage; g lucocorticoids , hypertonic solutions Cytotoxic edema: The swelling of cellular elements; Hypoxia/asphyxia, water intoxication, meningitis, encephalitis, Reye’s syndrome Interstitial edema : Attributed to increased water and sodium in periventricular white matter; Obstructive hydrocephalus; Surgical shunting, acetazolamide

CSF sampling:

CSF sampling Contraindication or precaution in ↑ICP Pressure from lumbar puncture: 65-195 mm CSF (H 2 O), or 5 – 15 mmHg Cells: 0; ↑ by inflammation, tumor, or other cerebral damage Protein: < 35 mg/dl; ↑ in blockage or increased BBB permeability. Glucose: > 40 mg/dl; ↓ in meningeal tumor, fungal or TB infection, sarcoidosis Appearance: not cloudy or xanthochromic

Function of CSF:

Function of CSF Maintenance of a constant external environment for neurons and glia Mechanical cushion to protect the brain and provide buoyancy to the heavy brain (1400 g) Serves as a lymphatic system and a conduit for neuropeptides pH of CSF regulates pulmonary ventilation and CBF

Function of CSF:

Function of CSF Maintenance of a constant external environment for neurons and glia Mechanical cushion to protect the brain and provide buoyancy to the heavy brain (1400 g) Serves as a lymphatic system and a conduit for neuropeptides pH of CSF regulates pulmonary ventilation and CBF

Functions and Properties of the BBB:

Functions and Properties of the BBB General Properties of the BBB Large molecules do not pass through the BBB easily. Low lipid (fat) soluble molecules do not penetrate into the brain. However, lipid soluble molecules rapidly cross the BBB into the brain. Molecules that have a high electrical charge to them are slowed . Therefore: The BBB is selectively permeable to :Oxygen, Carbon dioxide and glucose The BBB is not permeable to hydrogen ions

Function of CSF:

Function of CSF Maintenance of a constant external environment for neurons and glia Mechanical cushion to protect the brain and provide buoyancy to the heavy brain (1400 g) Serves as a lymphatic system and a conduit for neuropeptides pH of CSF regulates pulmonary ventilation and CBF