L21 Transport within the CNS Flashcards
list the fluid compartments in the CNS
Brain volume total = 1200 mL ICF = 720 mL ECF = 480 mL - Blood plasma = 70mL - Interstitial fluid = 260 mL - CSF = 90-140 mL
list the main constituents of the CSF compared to plasma
low in (compared to plasma) -pH, protein, glucose, K+ Ca+
high in (compared to plasma) -Na, Cl, Mg2+
what are the functions of CSF?
- maintaining constant extracellular environment
- removal of metabolites from brain
- changes in CSF pH = influences pulmonary ventilation rate and cerebral blood flow
- cushion between brain and skill (shock absorption + buoyancy)
where does CSF circulate?
- Ventricles
lateral ventricles – foramen of Monroe – 3rd ventricle – cerebral aqueduct — 4th ventricle — lushka and magendie - spinal canal
- subarachnoid space
where does CSF travel after the 4th ventricle?
passes into the subarachnoid space and central spinal canal
at what level is a lumbar puncture/spinal tap performed?
L3/L4 levels in adult
L4/L5 level in children
what can spinal tap/lumbar puncture diagnose? what is the normal value?
infections - meningitis
stroke
spinal cord tumor
cancer in CNS
65-200 mm water/ 5-15 mmHg
describe the site of the BBB
endothelial cells - with tight junctions in between
astrocyte endfeet
capillary basement membrane
transcellular routes through endothelial cells
allows gases and glucose uptake
what are the mechanisms of solute transport across the BBB
transcellular only!
what does the rate of transcellular transport depend on?
lipid solubility - the higher the oil/water partition coefficient is, the better transfer through phospholipid membranes
what things can diffuse through BBB?
blood gases small hydrophobic molecules small uncharged bipolar molecules water glycerol urea
how does glucose and L-DOPA get into brain?
facilitated diffusion
Glucose – GLUT 1 transporter (faster)
L-DOPA transporter - carrier for neutral aa
how does glycine get into the BBB from the brain into the blood?
secondary active transport – co transport with Na+
what things can cause the BBB to become permeable (endothelial cell shrink - tight junctions open)?
- htn
- hyperosmolality
- inection - HIV
- trauma, ischemia, inflammation, pressure
- toxic compounds, metals (Pb2+)
- lymphocytes can cross over from blood to brain - chemokine receptors involved CCR5
- they open BBB if they want to intro lipid insoluble drugs to CNS
what organs are affected with a permeable BBB?
circumventricular organs
- area posterma
- pineal body
- subcommissural organ
- subfornical organ
- organum vasculosum of lamina terminals (OVLT)
- neurohypophysis
- median eminence
describe the site of the blood-CSF barrier
ventricular lining
-ependymal cells (group 2) + gap junctions
choroid plexus
-secretory ependymal cells (group 1) - produce CSF ++ tight junctions
distinguish between mech. of solute (and water) transfer across BBB and blood-CSF barrier and those operating across the ependymal cells lining the ventricles
basolateral membrane - co transporters for Na+, K+, Cl-
Apical membrane microvilli - co transporters for K+ and Cl-…. Na+, K+ and Cl- ion channels…. Na/K pump
ions are accompanies by transport of water by local osmosis
where is CSF absorbed and returned to venous circulation?
by arachnoid granules in lumen of superior sagittal sinus
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from bacterial meningitis?
- cells in CSF = high polymorphonuclear neutrophils/leukocytes 1000/<5
- protein = high 500/35
- glucose = low 20/60
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from viral meningitis
- cells in CSF = high lymphocytes 500/<5
- protein = high 500/35
- glucose = normal
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from brain tumor or abscess
- cells in CSF = high lymphocytes 500/<5
- protein = high 500/35
- glucose = normal (sometimes can be lower)
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from multiple sclerosis
- cells in CSF =normal, but IgG increased + changes in T lymphocytes!
- protein = normal
- glucose = normal
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from Guillain-Barre syndrome
- cells in CSF = 50/35
- glucose = normal
list the main disturbances in the composition of the CSF (cells in CSF, protein, glucose) obtained from pt suffering from Subarachnoid hemorrhage
- cells in CSF = RBCs
- protein = high
- glucose = normal
what is the cause of communicating hydrocephalus?
- Due to malabsorption of CSF due to thickening of the arachnoid villi due to several pathologies
- Enlargement of ALL ventricles will always occur in communicating
- PAPILLOMAS: tumors of the choroid plexus can (but rarely) cause communicating by secreting CSF in great excess
- excess CSF secretion unmatched by rate of CSF drainage - increase ICP
what is the cause of non-communicating hydrocephalus?
- Due to blockage of CSF flow thus an enlargement of the ventricles above the blockage
- Enlargement of the Lateral Ventricles ALWAYS occurs in non-communicating/obstructive
what is normal pressure hydrocephalus?
- symptoms are aging/loss of cognitive ability, disturbances of walking and urinary incontinence
- enlarged ventricles, sulci, fissures with a flattening of cortical gyri against skull
- reduction in brain volume
- decrease in cellular volume of brain
what does the Monroe-Kellie doctrine state?
if there is a tendency for a fluid compartment of the brain to increase (e.g. tumor, abscess) there must be a corresponding decrease in another compartment or ICP will rise!
what is the cause of vasogenic brain edema?
- origin = increase cap. permeability
- location = W and G matter
- composition of edema fluid = plasma filtrate (with proteins)
- cap permeability to large mol. = increased
- disorders = brain tumor, abscess, trauma, hemorrhage
what is the cause of cytotoxic brain edema?
- origin = **neuronal and glial swelling - why? - blood supply, oxygen/glucose = low, ATP and Na/K pump tired, ion gradients fucked up
- location = W and G matter
- composition of edema fluid = increased intracel. water and Na
- cap permeability to large mol. = normal
- disorders = hypoxia, water intoxication, ischemia
how do tumor get blood supply?
paracellular transport
what is congenital hydrocephalus?
- cerebral aqueduct blocked/not formed - dilate lateral ventricles
- dandy-walker syndrome - foramen of lushka and magendie not developed - dilation of all ventricles
what increases ICP
- hydrocephalus
- tumor growth
- IC hemorrhage
what are symptoms of ICP increases?
- nausea
- bradycardia
- systemic htn
- loss of consciousness
- papilledema (optic disc swelling )
what decreases ICP
head injury
dehydration
spinal tumor