1. Learning outcomes
   1. Functions of CSF
   2. Formations of CSF
      1. Site
      2. Mechanism
      3. Composition & Disease
      4. Volume
      5. Distribution & Flow
      6. Flow & Hydrocephalus
   3. BBB
      1. Function
      2. Barrier and CNS disease
   4. ICP
      1. Determinants
      2. Dangers of a rise
      3. Cushing's relfex
      4. Causes of rise
2. BBB
   1. Formed by the walls of cerebral capillaries,assoc.transporters & astrocytes
   2. Regulates entry of substances into brain cells & interstitial fluid from blood
   3. Single layer of flattened endothelial cells of capillary connected by tight junctions, surrounded by basement membrane & astrocytes
   4. Acts as continuous sheath of tissue covering & sealing the capillary wall
   5. Restricts free movement of subtances from blood into brain interstitial fluid
   6. Function : to maintain constant environment for the neurons of CNS
   7. Importance
      1. Permeability required for effective Tx of CNS dz
      2. Avoidance of CNS S/E of drugs
      3. Neurooncology
3. Manifestations of a rise in ICP
   1. Initially, Headache,nausea,restlessness
   2. worsens; neural dysfunction, papilloedema
   3. As ICP rises further, cerebral perfusion is low -> cushings reflex
4. ICP
   1. Normally maintained at about 10 mmHg
   2. if volume of cranial contents increase, ICP increase
   3. dangers-> cerebral vessels compressed -> cerebral blood flow reduces -> cerebral ischaemia
5. Cushing's Reflex
   1. Patophysiological reflex
   2. oocurs when cerebral perfusion decreases considerably & brain become severely hypercapnic & hypoxic
   3. Hypercapnia mainly but also hypoxia directly stimulate vasomotor centre in medulla
   4. Hypercapnic stimulation of medullary vasomotor centre
   5. Cerebral perfusion improved
   6. Increased arterial blood P
   7. Increased firing in baroreceptor afferents
   8. Activity of cardio-inhibitory centre increases
   9. Reflex bradycardia
   10. End Result
       1. Elevated arterial blood P accompanied by bradycardia
       2. This is an ominous sign in patients wth head injury/suspected brain tumour
       3. Indicates large increase in ICP
6. CSF
   1. Clear,Colourless fluid, few white blood cell, no red blood cells, v.little protein
   2. fills subarachnoid space & ventricles
   3. Functions
      1. Supports & provide mechanical cushioning for brain
      2. Cushioning effect allows brain to withstand normal minor traumas associated with everyday living
   4. Site
      1. Formed by tuft of capillaries & assoc. membranes which invaginate lateral,3rd,4th ventricles (Choroid plexus)
      2. Choroid plexus forms 70% of CSF
   5. Charecteristic
      1. Wall of choroid plexus
         1. Endothelial cells of the capillary wall
         2. Epithelial cells (ependema) surrounding the capillary
         3. Epithelial cells surrounding the capillaries --> connected by tight junctions
         4. therefore acts as a continuous sheath of tissue covering & sealing the capillary wall
            1. therefore acts as a continuous sheath of tissue covering & sealing the capillary wall
         5. Restricts free movement of subtances from blood into CSF
      2. V.low permeability to lipid-insoluble solutes
         1. e.g ions,glucose,AA
         2. Restricted movement & tightly regulated
         3. Movement depends on presence of transporter in the walls of ependema (e,g GLUT1)
      3. Permeability to lipid soluble solutes
         1. e.g fats,sterols,O2,CO2,lipid soluble drugs,anaesthetic
         2. Free & unrestricted movement
         3. Lipid soluble solutes dissolve in cell membrane of capillary endothelial & ependymal cell
   6. Composition
      1. [Na] & [CL] > than plasma
         1. Topic
      2. [K] < than plasma
      3. [Glucose] < than plasma
      4. Almost no protein
   7. Blood-CSF barrier
      1. formed by choroid plexus & certain brain capillaries & assoc. transporters
      2. Transporters promote entry of others into CSF from blood, therefore barrier regulates entry of subtances from blood into CSF
   8. Volume
      1. Total 140ml, Sub Arachnoid space: 117ml, Ventricles: 23ml, Vol is constant , Rate of secretion=rate of absorption
   9. Flow
      1. Lat Ventricles -> 3rd -> 4th -> Subarachnoid space -> absorption by bulk flow into arachnoid vili
   10. Hydrocephalus
       1. Increase in CSF volume -> obstruction to CSF flow at any point
       2. Results in enlargement of ventricles
       3. Brain becomes flattened agaisnt skull leading to brain damage
       4. Types
          1. Infantile: Stenosis/inflammation of aquaduct of sylvius (congenital/acquired)
          2. Adult: Obstruction of aquaduct of sylvius/obstruction from 4th ventricle