Cerebro Spinal Fluid and the Blood-Brain-Barrier

1. Brain metabolism

is very high; amounts to 15% of total body metabolism although it only weighs 2% of total body weight

2. Perfusion:

Perfusion is about 700-900 ml/min (or about 15% cardiac output)

3. Metabolism:

There is no anaerobic metabolism in the brain (no glycogen storage and no oxygen storage)

4. Aerobic metabolism:

There is only aerobic metabolism with O2 and glucose immediately required from the blood. If the blood flow is stopped -> unconscious with 3-4 seconds.

4b.

In contrast to other body cells, glucose uptake by neural cells is not dependent on insulin. Therefore, a diabetic will have no mental problems.

5. Blood Flow Regulation:

Practically and totally autoregulated (pO2, PCO2 and pH dominated)

6. Blood Brain Barrier:

Barrier between blood and brain tissue. This barrier is caused by tight junctions between the brain capillaries. In addition, there is little pinocytic activity and there are membrane-bound enzymes to destroy hormones and neuro-transmitters that may attempt to cross the barrier.

7.

Easily transported: lipid-soluble such as O2, CO2, water, anesthetics

Medium transportable: electrolytes (charge!)

Difficult transportable: proteins, non-lipid solubles

8.

8. Some brain areas have sensory receptors (temperature, osmotic receptors, glucose, hormones, etc) and need to be in contact with blood. Those areas, which therefore have little or no BBB, are: a. areas in hypothalamus b. area postrema (vomiting!) c. pineal gland

9.

Evidence is emerging that BBB is not static but can be influenced. For example, several diseases (such as meningitis) may decrease BBB (which would allow penicillin to reach brain tissue!).

10.

Also, in (premature) babies, the BBB is not complete yet!

1.

CSF is required to nourish brain tissue and to protect the brain from blows to the head (floating brain), together with the skull. However, because of the inertia of the fluid and the brain, there is a potential danger of the “contrecoup” (brain damage at the other side of the blow).

Typical; a boxer will have most damages in the occipital cortex -> partial blindness.

2.

CSF is produced by the choroid plexuses located in all four ventricles, most in the lateral ventricles.

Every day about 500 ml CSF is produced.

The total quantity in a normal brain is about 150 ml; there is therefore a 3-4x daily renewal of all CSF.

3.

CSF flows from the Lateral ventricles, through the foramen of Monro into the Third ventricle and, through the Aqueduct of Sylvius, into the Fourth ventricle. This ventricle is connected though two foramina of Luschka and the foramen of Magendie into the Cisterna Magna. From there, fluid flows through the (sub)arachnoidal space and reaches the arachnoidal villi.

4.

The arachnoidal villi are actually valves between the brain fluid and the venous system. If the brain fluid pressure is higher than the local venous pressure (about 10 mm Hg), then CSF will flow into the veins and back to the heart.

5.

Measuring CSF pressure is done with a spinal tap. Buf before you do this, you MUST check for one thing!!

The absence of papilledema. (indication of raised intracranial pressure -> risk of hernation of the brain stem -> acute death.

5b.

The sclera of the eye is connected by dura with the dura of the brain, which runs along the optic nerve. So, if the cerebral pressure is increased, then the pressure around the optic nerve is increased and also at the exit of the optic nerve from the eye; the papill.

5c.

The pressure in the eye is normal. Therefore the high pressure in brain/optic nerve will push fluid into the papil. Also, this high pressure will impede venous flow from the retina. Together, this causes papilledema.

6.

Spinal tap: Patient lies sideways and horizontal. A spinal needle is inserted in the lumbar spinal canal. The needle is connected to a long transparent tube that is open at the top. Normal CSF pressure: 130 mm (= 10 mmHg)

7.

Why check? Because if the cerebral pressure is high, then this may cause herniation of the medulla into the spinal canal -> acute death!

8.

With a spinal tap, you can also do the Queckenstedt test! (= blocking the jugular veins will impede the exit of cerebrospinal fluid through the arachnoidal villi which will immediately increase the cerebrospinal pressure! Used in the old days to detect spinal stenosis).

1. Literally:

too much water in the brain!

2. Non-communicating hydrocephalus:

block in one of the canals so that CSF is still produced but cannot flow to the arachnoidal space. Usually the block is located in the aqueduct of Sylvius (atresia (closure) before birth or by a tumor at any age).

3. Communicating hydrocephalus:

fluid is not transported to and through the arachnoidal villi because these are blocked (caused by debris blockage from an infection, inflammation or bleeding).

3a.

Therefore, the pressure is increased throughout the cranium. Another reason for increase in cranial pressure is a large tumour.

3b.

In both cases, the high pressure will flatten the brain tissue in a thin layer against the skull. In neonates, because the skull bones are not yet fused, the whole head swells.

Therapy:

Insert a shunt from the brain (ventricles) to another space in the body (peritoneal cavity, right atrium). Insert a

1.
This is a very dangerous situation!
Because the brain is located in a solid vault (=bank), oedema will increase the intra-cranial pressure. This will compress the blood vessels -> reduce blood flow and destroy brain tissue.

2.

Typical (and common) example: brain concussion. Trauma causes capillaries to leak fluid -> oedema -> pressure increase -> ischemia -> more damage -> more leakage -> more pressure; Vicious circle!

3.
Heroic measures are now required to save the brain:

1. Puncture the ventricles -> removal of excess fluid

4.

1. Infusion in blood with a concentrated osmotic substance (mannitol). This will lead to an increase the oncotic pressure. When this becomes high enough, the filtration pressure in the brain capillaries will become negative -> removal of the interstitial fluid (remember the Starling exchange system?).