Regulation of Blood Flow / Blood Brain Barrier

Question 1

unconsciousness will result If CBF is interrupted for as little as …

Answer 1

4 seconds

Question 2

What is SYNCOPE

Answer 2

Fainting

Question 3

Causes of syncope? (5 -> resulting in?)

Answer 3

including low BP, postural changes, vaso-vagal attack, sudden pain, emotional shock etc. resulting in temporary interruption/reduction of blood flow to the brain

Question 4

a VAST SURPLUS of glucose to the brain via the blood is important because….

Answer 4

the brain cannot store, synthesize or utilise any other source of energy (ketones to an extent during starvation)

Question 5

HYPOGLYCAEMIA can occur as a result of?

Answer 5

• Poorly managed diabetes

Question 6

Symptoms of hypoglycaemia? (3)

Answer 6

• Disorientation, slurred speech, impaired motor function

Question 7

What is the level of blood glucose for unconsciousness

Answer 7

below 2mM

Question 8

2 mechanistic targets of regulation of blood flow to brain?

Answer 8

1. Mechanisms affecting total cerebral blood flow

2. Mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow

Question 9

How is TOTAL CEREBRAL BLOOD FLOW regulated? what is the BP kept between?

Answer 9

Autoregulated, Kept between MABP of 60-160mmHg

Question 10

What changes take place in high and low pressure blood flow to the brain to VSMC?

Answer 10

• Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP

Question 11

LOCAL CEREBRAL BLOOD FLOW 2 ways of control?

Answer 11

• Neural control

- Chemical control

Question 12

4 neural factors that affect cerebral blood flow resulting in vasoconstriction/dilation?

Answer 12

1. Sympathetic nerve stimulation- vasoconstriction
2. Parasympathetic nerve stimulation- vasodilation
3. Central cortical neurones- releasing vasoconstrictor neurotransmitters e.g. catecholamines
4. Dopaminergic neurones- vasoconstriction

Question 13

How do DOPAMINERGIC NEURONES control blood flow? What do they innervate? What do they do? What effect does dopamine have?

Answer 13

• Innervate penetrating arterioles and pericytes around capillaries (pericytes are cells that wrap around capillaries and can be contractile)
• May participate in diversion of cerebral blood flow to areas of high activity
• Dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors

Question 14

PATTERN OF VASCULARISATION of the brain? where do the arteries come from? where do the veins go? (think layers)

Answer 14

• Arteries on the pial surface of the meninges produce branches that penetrate down into the parenchyma to form capillaries
• These drain into venules which drain into pial veins

Question 15

Chemical factors that influence local cerebral blood flow and their effect and do they cross the BBB or are they generated in the brain?? (7)

Answer 15

1. CO2 (indirect- it actually affects pH via carbonic anhydrase and produces H+ ions)- vasodilator (CROSSES)
2. pH (H+, lactic acid etc.)- vasodilator (DOESNT CROSS)
3. Nitric oxide- vasodilator
4. K+- vasodilator
5. Adenosine- vasodilator
6. Anoxia- vasodilator
7. Other (kinins, prostaglandins, histamine, endothelins)

Question 16

What does the choroid plexus do

Answer 16

Produce CSF

Question 17

What is the choroid plexus

Answer 17

Some regions in the ventricles where ependymal cells are modified to form branched villus structures. This is the choroid plexus

Question 18

Describe the formation of CSF

Answer 18

• Capillaries are leaky, but adjacent ependymal cells have tight junctions at the plexus- not at all leaky
• Choroid plexus ependymal cells secretes CSF into ventricles and it circulates (route of circulation in a previous lecture)

Question 19

Route of circulation of the CSF? (7)

Answer 19

o Lateral Ventricles
o 3rd Ventricle (via interventricular foramina)
o Cerebral Aqueduct
o 4th Ventricle
o Subarachnoid Space (via medial and lateral apertures)
 These openings lead to the subarachnoid space so have a continuous connection between ventricles and subarachnoid space.
o The fluid as its being produced will leak back into the venous system e.g. superior sagittal sinus via arachnoid granulations.
o It circulates around.

Question 20

3 functions of the CSF?

Answer 20

o Protection (chemical and physical)
o Nutrition of neurones
o Transport of molecules

Question 21

What is molecules are lacking in CSF?

Answer 21

protein

Question 22

Levels in CSF compared to blood of:
K
Mg
Ca

Answer 22

K - lowered
Mg - higher
Ca - lower

Question 23

• The pH of the CSF is slightly more X

Answer 23

ACIDIC

Question 24

• OSMOLARITY OF the CSF IS XX

Answer 24

THE SAME

Question 25

BBB - THE CAPILLARIES OF THE CNS PARENCHYMA DERIVED FROM XXX

Answer 25

SURFACE PIAL CELLS

Question 26

Where is the BBB found?

Answer 26

Capillaries of the CNS

Question 27

4 differences between BBB and normal capillaries?

Answer 27

BBB capillaries have little/no transcellular vesicular transport their inter-endothelial tight junctions are much less leaky - BBB capillaries have much denser pericyte coverage - BBB capillaries are covered with “END FEET” from astrocytes (the ends of some of the astrocyte processes)

Question 28

What type of molecules cross the BBB easily

Answer 28

- LIPOPHILIC molecules (O2, CO2, alcohol, anaesthetics?)

Question 29

How do water, glucose, amino acids and electrolytes cross the BBB?

Answer 29

WATER AQP1/AQP4 channels GLUCOSE GLUT1 transporter proteins AMINO ACIDS 3 different transporters ELECTROLYTES Specific transporter systems

Question 30

Type of capillary in the circumventricular organs?

Answer 30

fenestrated

Question 31

capillaries in the circumventricular organs are generally involved in...

Answer 31

secreting into the circulation, or sampling plasma

Question 32

1. The BBB breaks down in many pathological state such as? (4)

Answer 32

Inflammation, infection, trauma, stroke

Question 33

1st gen histamines [can/can't] cross the BBB

Answer 33

can

Question 34

why cant 2nd gen antihistamines cross the BBB, and why is this useful

Answer 34

because they are polar, so they don't cause drowsiness

Question 35

How is issue of dopamine being unable to cross the BBB sorted in Parkinsons

Answer 35

- L-DOPA can cross the BBB via an AA transporter, and is converted to dopamine in the brain

Question 36

What do we administer with LDOPA and why

Answer 36

We co-administer L-DOPA with CARBIDOPA, a DOPA decarboxylase inhibitor to prevent peripheral breakdown of dopamine