Transport Within CNS

Question 1

What are the fluid compartments of the CNS?

Answer 1

1. Intracellular
2. Extracellular
   a. Plasma
   b. Interstitial
   c. CSF
   a. Intraventricular b. Subarachnoi

Question 2

Describe CNS fluid distribution

Answer 2

• Produced by secretion via choroid plexus

• Circulates within a defined anatomical space
– Ventricles, central canal (bulbar and spinal), subarachnoid space

Blood plasma- 70 ml

Interstitial fluid- 260 ml

CSF- 90-140 ml

Question 3

Give the CSF functions

Answer 3

Maintenance of a constant EC fluid environment

• Removal of metabolites from the brain

• Regulation of the rate of pulmonary ventilation (change in pH) and cerebral blood flow (CBF)
Cerebral Perfusion Pressure = MAP - ICP

• Cushioning and protection of the brain (reducing chances for contact with skull)
– Buoyancy: weight of brain reduced from ~1400 gm to ~50 gm, decreasing pressure on basal structures

Question 4

What is a lumbar puncture?

Answer 4

• Location of spinal tap – Adults: L3/L4
– Children: L4/L5

• Diagnosticpurposes
– Estimate of ICP
• NormalICP:5-15mmHg

Question 5

Explain the pathological elevation of ICP

Answer 5

• Hydrocephalus: Increased fluid within/around the brain

• ICP measurement
– Ventricular catheter (most accurate)
– Subdural screw/bolt
– Epidural pressure sensor (no drainage option)

• Pathologically elevated ICP: > 15 mmHg (200 mmH2O)

• Adverse effects of a rise in ICP
– Nausea
– Increased blood pressure (systemic hypertension)
– Bradycardia
– Papilledema

Question 6

What is the blood brain barrier made up of?

Answer 6

Tight junctions between endothelial cells

Astrocytuc end feet

Question 7

Describe the transport mechanism of the blood brain barrier for transcellular transport

Answer 7

Diffusion rate across the bilayer depends on lipid solubility.

Because the paracellular route is closed, substances must pass via the transcellular route. Most of the cell membrane is occupied by the phospholipid bilayer component. Transport across this bilayer commonly depends on the solute’s solubility in lipid.
Solutes that readily dissolve in lipid will cross the endothelial cell membranes. The oil/water partition coefficient expresses the degree to which solutes will move into lipid from an aqueous environment. The higher the coefficient is, the more effective the transfer from water to lipid will be. Small hydrophobic molecules, blood gases, small uncharged polar molecules, water, urea and glycerol all diffuse readily across phospholipid bilayer.

The line in the graph above shows the expected relative extraction of solute from cerebral blood into brain tissue as a function of the partition coefficient. Note that glucose and L-dopa do not lie on the curve. Glucose is transported into the brain via GLUT1 transporters (facilitated diffusion) and L-Dopa through a neutral amino acid carrier.

Phenobarbitol, while highly lipophilic, has a relatively low extraction ratio. This is because the substance is pumped out of the brain by an ATPase-dependent transporter

Question 8

What are the transport mechanisms across the BBB?

Answer 8

• Diffusion, facilitated diffusion and active transport
– Lipid soluble molecules diffuse across the BBB via the
phospholipid part of the endothelial cell membranes

– Glucose crosses the BBB by facilitated diffusion via a transporter GLUT1 in the endothelial cell membranes

– L-dopa (dopamine precursor) also crosses the BBB by facilitated diffusion, via a carrier for neutral amino acids

– Glycine crosses the BBB (from brain to blood) via secondary active co-transport with Na+, causing transfer of glycine in a Na+-dependent fashion

Question 9

What are the causes of increasing BBB permeability?

Answer 9

• Hypertension
• Hyperosmolality
• Infection
• Trauma, ischemia, inflammation

Question 10

What are the circumventricular organs?

Answer 10

• Brain regions where capillary endothelial cells lack tight junctions

• Regions where access of neurons to blood plasma is crucial for function (sensory or secretory)
– E.g., blood pressure and osmolarity detection by the subfornical organ

Question 11

Describe secretion and circulation of CSF

Answer 11

The Ventricular Lining is not Uniform in Structure and Function.

• CSF is absorbed by arachnoid villi
• CSF pressure > venous pressure
• Arachnoid villi act as one-way valves
• CSF production ~ 500 ml/day
• Total CSF volume ~ 140 ml
• Replaced ~ every 7

Question 12

Wwhat is the most common type of hydrocephalus?

Answer 12

Noncommunicating (obstructive) hydrocephalus is the most frequent type due to blockage of the flow of CSF within the ventricular system. In this case CSF is unable pass between ventricles or to exit the ventricular system into the subarachnoid space, due to obstruction of interventricular foramina, cerebral aqueduct or outflow foramina of fourth ventricle.

Question 13

What is hydrocephalus Ex Vacuo?

Answer 13

Hydrocephalus ex vacuo is associated with neurodegenerative disease. Cellular loss, as is seen in Alzheimer’s and Huntington’s diseases, permits enlargement of ventricles, as CSF passively occupies ever-increasing ventricular volume.

Brai; tissue atrophy, increased CSF occupancy

Question 14

How does communicating hydrocephalus develop?

Answer 14

Mismatched abskrption and production of CSF —> enlargement of all vdntrciles

Question 15

What are the effects of communicating hydrocephalus with Normal. ICP?

Answer 15

• Episodic increase in ICP
• Expansion of ventricles distorts brain tissue
• Affects mainly the elderly

Question 16

WHat can lead to communicating hydrocephalus?

Answer 16

Communicating hydrocephalus can arise from impaired absorption of CFS by the superior sagittal sinus. This may reflect accumulations of cells in the subarachnoid space that impede passage of CSF through the arachnoid villi.

A rare form of communicating hydrocephalus results from tumors of choroid plexus (papillomas) with excess CSF secretion unmatched by rate of CSF drainage. Excess CSF secretion causes enlargement of all ventricles.

Question 17

What is the impact of edema to the brain?

Answer 17

Edema is an accumulation of fluid in the EC or IC space within the brain. Disturbances of blood supply that interfere with the normal well-regulated exchange of solutes and water between blood and brain, can cause edema. Edema may be local or general. Brain edema may be vasogenic or cytotoxic.

Vasogenic edema arises from damage to brain capillaries rendering them more permeable than normal, compromising the BBB, and allowing fluid to accumulate in the white matter and runs along axonal tracts (increase in IC fluid compartment). This could arise due to trauma or focal inflammation. Tumor-facilitated release of vasoactive and endothelial destructive compounds (e.g. arachidonic acid, excitatory neurotransmitters, eicosanoids, bradykinin, histamine, and free radicals).
Cytotoxic edema arises while the BBB remains intact and is caused by an inadequate blood supply to neurons and glia. When the Na/K pumps are deprived of ATP, the ionic gradients dissipate, and the cells swell with ensuing damage. Water intoxication is another source of cytotoxic edema.
During edema, the astroglial cells are capable of regulating their cellular volume after the initial swelling, and thus may suffer less damage than the other CNS cells. This renders them capable of regulating the neuronal microenvironment during the onset of damage. The most common treatment is osmot

Question 18

What is brain edema?

Answer 18

Increased CNS fluid volume and/or disturbance of blood supply. Osmotherapy is a key treatment

Question 19

Contrast cytoplasmic and vasoactivle orgig);

Question 20

Contrast cytotoxic and vasoactive brain edema. Location

Answer 20

Cytotoxic- grey and white matter

Question 21

Contrast composition of edema in vasogenic and cytotoxic

Answer 21

Vasogenic-plasma filtrate (with plasma proteins)

Cytotoxic- Increased intracellular water and Na+

Question 22

Contrast capillary permeability to large mol3cules in cytotoxic and vasogenic brain edema

Answer 22

Vasogenic- increased (compromised BBB)

Cytotoxic- normal (intact BBB)

Question 23

What clinical disorders of the different types of brain edema?

Answer 23

Vasogenic- brain tumors, absecess, trauma, hemorrhage

Cytotoxic- hypoxia, water intoxication, ischemia