Central Blood Flow Regulation and the Blood-Brain Barrier Flashcards
How much oxygen is supplied to the brain per minute?
55 ml/100g of tissue/min
Why is there a vast surplus of glucose delivery to the brain?
Because the brain can only metabolise glucose
In starvation, ketone bodies can be metabolized if there is a shortage of glucose but glucose is the main nutrient
How does a reduction in blood flow to the brain initially manifest?
As syncope (fainting)
Blood glucose below what value will lead to loss of consciousness, coma and death? What are normal fasting levels?
2 mM
Normal fasting levels: 4-6mM
Between what range in mean arterial blood pressure can autoregulation maintain a constant cerebral blood flow?
60-160 mm Hg
Extra notes:
- Over this range arteries and arterioles dilate or contract to maintain blood flow.
- Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP.
- Below this autoregulatory pressure=insufficient supply –> compromised brain function
- Above this autoregulatory pressure range= increased flow–>swelling of brain tissue not accommodated by the “closed” cranium –>intracranial pressure increases – dangerous.
Name one important factor to do with the smooth muscle lining arterioles that allows regulation of blood flow.
Myogenic Mechanism – when the smooth muscle surrounding arterioles is stretched, it will contract to maintain a constant blood flow
This occurs when there is a change in blood pressure in the body
What are the two types of control of cerebral blood flow regulation?
Neural and Chemical Control
Describe the vascularisation pattern in CNS tissues.
Surface pial vessel branches
Penetrate into brain parenchyma
Branch into caillaries then drain into venules and veins and to the surface pial veins
What are the four types of neural control of cerebral blood flow?
- Sympathetic innervation of the main cerebral arteries – causes vasoconstriction only when arterial blood pressure is high
- Parasympathetic (facial nerve) stimulation – can cause a little bit of vasodilation
- Central cortical neurons – neurons within the brain itself can release neurotransmitters such as catecholamines that cause vasoconstriction (e.g A, NA)
- Dopaminergic neurons – produce vasoconstriction (important in regulating localised blood flow to areas of the brain that are more active)
What feature do capillaries in the brain have that allow them to contract?
They are surrounded by pericytes, which are contractile cells
They have several functions e.g. contractile, immune function, transport properties
What do the dopaminergic neurons affecting cerebral blood flow innervate?
Pericytes around capillaries and smooth muscle around arterioles
They participate in diversion of cerebral blood flow to areas of high activity - local effect
Dopaminergic neurons cause contraction of pericytes via which receptors?
Aminergic and serotoninergic neurons
Which fibres innervate the main arteries in the brain?
Sympathetic fibres
Name some chemical factors that increase blood flow to particular tissues.
How does change in pH affect blood flow?
The lower the pH (the higher the H+ concentration) the more the vessel vasodilates
Describe how carbon dioxide indirectly causes vasodilation in the cerebral vessels.
- H+ ions can’t cross the blood-brain barrier but carbon dioxide can
- Carbon dioxide moves from the blood through the blood-brain barrier into the smooth muscle cells
- Within the smooth muscle cells, in the presence of carbonic anhydrase, the carbon dioxide reacts with water to form bicarbonate and H+ ions
- These internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)
Where is CSF produced?
Choroid plexus – these are specific cells associated with the ventricles (in particular the lateral ventricles)
The ependymal cells are modified in some regions of the ventricles to form branched villus structures called the choroid plexus
Label the ventricles of the brain.
The ventricles, aqueducts and canals of the brain are lined with ependymal cells (epithelial-like glial cells, often ciliated).
Describe the passage of CSF through the ventricular system.
- CSF is produced by specialized ependymal cells of the choroid plexus (mainly in the lateral ventricles)
- From the lateral ventricles it goes through the foramen of Monro to the 3rd ventricle (via interventricular foramina)
- From the 3rd ventricles, CSF flows down the cerebral aqueduct to the 4th ventricle
- From the 4th ventricle it enters the subarachnoid space (via medial and lateral apertures) and eventually drains back into the venous system via arachnoid granulation
Compare the components of plasma and CSF. Why is this information important?
Big difference in potassium, magnesium, calcium and amino acids.
Proteins can indicate brain injury or infection.
What are the three types of capillaries? What percentage of all blood is in the capillaries at any one time?
40%
Continuous(moderately leaky), fenestrated(leaky), sinusoid(very leaky)
Describe the structure of the blood-brain barrier. Which cells areinvolved?
- The capillaries in the brain (derived from surface pial cells) have extensive interendothelial tight junctions, massively reducing solute and fluid leak across the capillary wall
- The capillaries are also almost entirely surrounded by pericytes (important in maintaining capillary integrity and function)
- Also surrounded by end-feet from astrocytes running along the capillary wall (important in maintaining BBB properties)
Peripheral capillaries have sparse pericyte coverage.
Name three circumventricular organs.
- Neurohypophysis (posterior pituitary)
- Subfornical organ
- Subcommisural organ
- Pineal body
- Area postrema
- Organum vasculosum of the lamina terminalis (OVLT)
This is where capillaries lack BBB properties(fenestrated therefore leaky CVO vessels). Found close to ventricles.
Why could dopamine not be administered peripherally as Parkinson’s treatment? What was the solution?
- Dopamine = cannot cross BBB.
- L-DOPA can cross via an amino acid transporter and is then converted to dopamine in brain
- BUT this was getting converted peripherally too so was co-administered with DOPA decarboxylase inhibitor (Carbidopa) which could not cross BBB, preventing peripheral conversion.
