BLOOD BRAIN BARRIER BBB
- Tight junctions of capillary endothelium in all nervous tissue and the epithelial cells of choroids plexus where capillary endothelium has gaps.
- Barrier to:
- Partially to smaller to smaller molecules e.g. billirubin in fetus – proportional to lipid solubility and inversely proportional to size.
- But carrier systems allow active transport of substances, which the barriers would otherwise not allow in. thus
“barrier” not very accurate as it also means transport barrier.
BRAIN TO BLOOD TRANSPORT
- Brain to blood transport- freer than from blood to brain thus:
- If large volume of CSF from brain to venous blood via arachnoid villi • Carrier systems, which move stuff from brain into blood capillaries.
- Brain permeability.
- O2, CO2 and H2O enter easily.
- Lipid solvent and unbound steroid hormone enter freely.
- Very low penetration by polypeptides and protein bound hormones.
- Bicarbonate and hydrogen ions enter very slowly while CO2 enters very fast. This is because there are chemoreceptors that respond to [H+]
- Glucose- passive slow entry. Active transport via the two GLUT 1(GLUT 155K and GLUT1 – 45K).
- Both encoded by same gene
- GLUT1-55K present in high amounts in capillaries
- Congenital deficiency of GLUT 1- low CSF glucose in infants with fits and retarded development.
TRANSPORT OF OTHER CHEMICALS
- In cerebral capillaries
- Stimulated by ET1 and ET3
- Induced by hormones from astrocytes.
- Keeps brain K+ low.
Other transporters for:
- Thyroid hormones
- Organic acid
- Nucleic acid precursors
- Basic, acidic and neutral amino acid.
CIRCUMVENTRICULAR ORGANS (CVOs)
- Posterior pituitary and part of median eminence
- Area postrema
FUNCTIONS OF THE CVOs
- Some function as neuro-hormonal organs i.e. where nerve cells produce neuro-peptides enter blood e.g. ADH and oxytocin and releasing factor from hypothalamus.
- Other are chemoreceptor zones e.g. area postremavomiting trigger from chemicals and plasma and OVLT &SFO- angiotensin and thirst.
- OVLT-site for osmoreceptors that controls ADH release.
- Also site for fever production i.e. circumventricular organs enable IL_1 to cause fever.
FUNCTIONS OF THE BBB
Functions of BBB in general
- Stricter control of internal environment and protection from fluctuation of electrolyte and chemicals.
- NB brain very sensitive to [H+], [Ca2+], [Mg2+] and [K+].
- Protection of brain from exogenous and endogenous toxins.
Fetus and BBB
- Fetal jaundice:
- Immature conjugating liver mechanism
- Immature BBB-Kernicterus thus basal ganglia inhibitioncrigler-najjar syndrome
- In adults with deficiency in glucoronly transferase- very high bilirubin and encephalopathy.
CLINICAL SIGNIFICANCE OF THE BBB
Drugs and BBB:
- drugs enter with difficulty/ease.
- Some antibiotics don’t while others do. Amines e.g. dopamine and 5HT hardly enter but acid precursors do so very fast e.g. L-DOPA, 5_hydroxytryptophan Infection and injury break the BBB.
- Tumor blood vessels have no astrocyte feet and so no BBB thus tight junctions not induced and also blood vessels are fenestrated in tumors. Lack of BBB- ease of diagnosis (location) e.g. radiology iodine will go in and light up the tumor Hypertension:
- Sudden increase in BP may destroy BBB. Hypertonic fluids:
- Increase of hypertonic fluids also destroys it.
- Hypothermia destroys BBB.
- VOL-150ML=15% brain volume
- 550ml/day i.e.3.7changes/day
- Choroids plexus-50-70%. Around blood vessels and ventricular walls 30-
- Arachnoid villi in sub arachnoid space-veins –cerebral venous sinuses.
- From foramina Magendie-median Lushka- lateral- to the sub-arachnoid space.
- NB. Spinal cord has similar villi to arachnoids around spinal routes.
- Direct flow (bulk flow) through villi- sinuses through valve mechanism500ml/day
- Rest by diffusion through cerebral blood vessels.
- Very low potassium and protein but more magnesium. Brain interstitial fluid=plasma
- Lumbar CSF
- (Lumbar puncture)
- Pressure 70-80mm CSF at 112mm
CSF=equilibrium pressure release & uptake. <68mm absorption stops.
- See table below ???
- Capacity of reabsorption by arachnoid villi- external or communicating hydrocephalus
- Circular block-internal hydrocephalus or non-communicating hydrocephalus.
- Toxoplasma gondii infection blocking Lushka Magendie
- Brain protein –low fluid whose surface tension holds arachnoid to dura (no space)-sub-dural
- Brain supports: blood vessels & arachnoids trabeculae
- Brain & arachnoids
- 1400gm in air-50gm in CSF hence need only light anchorage.
TRAUMA AND LUMBAR PUNCTURE
Blow on the head
• arachnoid slipping on dura & brain moves. CSF & arachnoid trabeculae cushion the movement.
Post –lumbar puncture pain
- thus fluid decrease leaves the brain hanging on blood vessels & nerve roots thus Stimulation of pain fibers.
- Treated by replacement of removed CSF with sterile isotonic saline.
- Trauma to the head
- skull fractures especially depressed ones
Contre coup injury–
• tear of blood vessels & bleeding-sub-dural.