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 Ketone bodies can be metabolized if there is a shortage of glucose but glucose is the main nutrient
Blood glucose below what value will lead to loss of consciousness, coma and death?
2 mM
On what levels do you get regulation of cerebral blood flow?
Mechanisms affecting total cerebral blood flow Mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow
Between what range in mean arterial blood pressure can autoregulation maintain a constant cerebral blood flow?
60-160 mm Hg
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
What are the four types of neural control of cerebral blood flow?
Sympathetic innervation of the main cerebral arteries – causes vasoconstriction 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 Dopaminergic neurons – produce vasoconstriction (important in regulating differential blood flow to areas of the brain that are more active)
What feature do capillaries in the brain have that allow them tocontract?
They are surrounded by pericytes, which are contractile cells They are a type of brain macrophage that 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
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.
Carbon dioxide NO pH Anoxia Adenosine K+ Other (e.g. kinins, prostaglandins, histamine, endothelins)
How does change in pH affect blood flow?
The lower the pH (the higher the H+ concentration) the more the vesselvasodilates
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 This internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)
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 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
Describe the structure of the blood-brain barrier. Which cells areinvolved?
The capillaries in the brain have endothelial cells with very tight junctions so there is tight control of what can pass through the wall of the capillary The capillaries are also surrounded by pericytes with end-feet runningalong the capillary wall When the pericytes contract they make it more likely for the molecules to leave the capillary
How does BBB affect parkinsons treatment
In parkinsons dopamine is reduced meaning so pharmacologically you want to increase dopamine. However you cant just give dopamine as it is polar. Therefore you give L-DOPA which can cross BBB via an amino acid transporter and is then converted to dopamine in brain.
Problem of L-DOPA
L-DOPA can be converted peripherally by DOPA decarboxylases in the blood. Therefore you give with Carbidopa a DOPA decarboxylase inhibitor which cant cross BBB
