Regulation of Blood Flow / Blood Brain Barrier Flashcards
unconsciousness will result If CBF is interrupted for as little as …
4 seconds
What is SYNCOPE
Fainting
Causes of syncope? (5 -> resulting in?)
including low BP, postural changes, vaso-vagal attack, sudden pain, emotional shock etc. resulting in temporary interruption/reduction of blood flow to the brain
a VAST SURPLUS of glucose to the brain via the blood is important because….
the brain cannot store, synthesize or utilise any other source of energy (ketones to an extent during starvation)
HYPOGLYCAEMIA can occur as a result of?
- Poorly managed diabetes
Symptoms of hypoglycaemia? (3)
- Disorientation, slurred speech, impaired motor function
What is the level of blood glucose for unconsciousness
below 2mM
2 mechanistic targets of regulation of blood flow to brain?
- Mechanisms affecting total cerebral blood flow
2. Mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow
How is TOTAL CEREBRAL BLOOD FLOW regulated? what is the BP kept between?
Autoregulated, Kept between MABP of 60-160mmHg
What changes take place in high and low pressure blood flow to the brain to VSMC?
- Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP
LOCAL CEREBRAL BLOOD FLOW 2 ways of control?
- Neural control
- Chemical control
4 neural factors that affect cerebral blood flow resulting in vasoconstriction/dilation?
- Sympathetic nerve stimulation- vasoconstriction
- Parasympathetic nerve stimulation- vasodilation
- Central cortical neurones- releasing vasoconstrictor neurotransmitters e.g. catecholamines
- Dopaminergic neurones- vasoconstriction
How do DOPAMINERGIC NEURONES control blood flow? What do they innervate? What do they do? What effect does dopamine have?
- 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
PATTERN OF VASCULARISATION of the brain? where do the arteries come from? where do the veins go? (think layers)
- 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
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)
- CO2 (indirect- it actually affects pH via carbonic anhydrase and produces H+ ions)- vasodilator (CROSSES)
- pH (H+, lactic acid etc.)- vasodilator (DOESNT CROSS)
- Nitric oxide- vasodilator
- K+- vasodilator
- Adenosine- vasodilator
- Anoxia- vasodilator
- Other (kinins, prostaglandins, histamine, endothelins)
What does the choroid plexus do
Produce CSF
What is the choroid plexus
Some regions in the ventricles where ependymal cells are modified to form branched villus structures. This is the choroid plexus
Describe the formation of CSF
- 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)
Route of circulation of the CSF? (7)
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.
3 functions of the CSF?
o Protection (chemical and physical)
o Nutrition of neurones
o Transport of molecules
What is molecules are lacking in CSF?
protein
Levels in CSF compared to blood of:
K
Mg
Ca
K - lowered
Mg - higher
Ca - lower
• The pH of the CSF is slightly more X
ACIDIC
• OSMOLARITY OF the CSF IS XX
THE SAME
BBB - THE CAPILLARIES OF THE CNS PARENCHYMA DERIVED FROM XXX
SURFACE PIAL CELLS
Where is the BBB found?
Capillaries of the CNS
4 differences between BBB and normal capillaries?
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)
What type of molecules cross the BBB easily
- LIPOPHILIC molecules (O2, CO2, alcohol, anaesthetics?)
How do water, glucose, amino acids and electrolytes cross the BBB?
WATER AQP1/AQP4 channels
GLUCOSE GLUT1 transporter proteins
AMINO ACIDS 3 different transporters
ELECTROLYTES Specific transporter systems
Type of capillary in the circumventricular organs?
fenestrated
capillaries in the circumventricular organs are generally involved in…
secreting into the circulation, or sampling plasma
- The BBB breaks down in many pathological state such as? (4)
Inflammation, infection, trauma, stroke
1st gen histamines [can/can’t] cross the BBB
can
why cant 2nd gen antihistamines cross the BBB, and why is this useful
because they are polar, so they don’t cause drowsiness
How is issue of dopamine being unable to cross the BBB sorted in Parkinsons
- L-DOPA can cross the BBB via an AA transporter, and is converted to dopamine in the brain
What do we administer with LDOPA and why
We co-administer L-DOPA with CARBIDOPA, a DOPA decarboxylase inhibitor to prevent peripheral breakdown of dopamine
