Regulation of blood flow; blood brain barrier Flashcards
Describe the oxygen supply to the brain?
HIGH - 55 ml/100 g tissue /min
15% of cardiac output
Whenever blood flow to the brain is reduced by more than 50%:
- you get insufficient oxygen delivery
- and brain function becomes impaired
If the total cerebral blood flow is interrupted for as little as 4 seconds, you will become unconscious
After a few minutes, irreversible damage will occur to the brain
Describe the glucose supply to the brain?
Normally a VAST SURPLUS of glucose to the brain via the blood
A supply of glucose is really important because the brain can’t synthesise or utilise any other source of energy
Ketones can be metabolised if there is a shortage of glucose but glucose is the main nutrient
Hypoglycaemia can lead to a loss of brain function
If the blood glucose concentration falls below 2 mM it can result in unconsciousness, coma and DEATH
How is cerebral blood flow regulated?
1) Mechanisms affecting total cerebral blood flow
2) Mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow - you need a system that can divert blood to the parts of the brain that really need it at the time
Describe the mechanisms affecting total cerebral blood flow?
Autoregulation occurs within a relatively wide breadth of the arterial blood pressure from 60 - 160 mm Hg
One Factor: MYOGENIC (response to stretch)
- The smooth muscle lining the arteries can stretch in response to blood flow
- An increase in pressure on the vessel wall will result in a myogenic response that leads to contraction of the smooth muscle - this decreases cerebral blood flow
- This myogenic response occurs when there is a change in blood pressure in the body
Also, the local delivery of oxygen to brain tissue is related to the needs of that tissue by local autoregulation
What are the two control mechanisms which regulate cerebral blood flow?
Neural control
Chemical control
Describe the neural control of the regulation of cerebral blood flow
Sympathetic Nerve Stimulation
- Sympathetic innervation of the main cerebral arteries can cause vasoconstriction - this only happens when the arterial blood pressure is HIGH
Parasympathetic (facial nerve) Stimulation
- We don’t normally associate the parasympathetic nervous system with vasculature
- However, facial nerve fibres are innervated by parasympathetic fibres - this causes a slight vasodilation
Central Cortical Neurones
- The neurones within the brain itself can release neurotransmitters such as catecholamines that cause vasoconstriction
Dopaminergic Neurones
- Produce vasoconstriction at arterioles and cappilaries
- They are important in regulating differential blood flow to areas of the brain that are more active
Describe dopaminergic neurones in the control of blood flow in the brain
NOTE: Capillaries in the brain have PERICYTES around them, which are contractile
- Pericytes are a type of brain macrophage
- They have a variety of functions e.g. immune function, transport properties, contractile
Dopaminergic neurones innervate the smooth muscle surrounding arterioles and the pericytes around the capillaries
When the dopaminergic neurones are active, they can cause the contraction of pericytes to decrease the blood flow to a particular area thus diverting blood to other, more active areas of the brain
Dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors
Describe the arrangement of arteries, arterioles and capillaries in the brain
See notes for diagram
The main arteries will be innervated by sympathetic fibres
Deeper down you get the arterioles with smooth muscle around them and the capillaries surrounded by pericytes
Innervation of the pericytes and arteriolar smooth muscle is how the dopaminergic neurones can regulate blood flow at a capillary level
Describe the chemical control of blood flow?
These are likely to be localised
They increase blood flow to particular tissues:
1) pH - when cells are active they will produce lactic acid - the H+ ions in the lactic acid will cause a drop in pH and cause vasodilation in that area
2) K+ is released at one stage of the action potential and acts as a vasodilator
3) CO2 is indirectly associated with vasodilation
Draw the graph of the effect of pCO2 on cerebral blood flow?
See graph
Sigmoid shape - increases pCO2 causes an increase in cerebral blood flow.
Describe how CO2 acts as a cerebral arterial vasodilator?
H+ ions DO NOT cross the BBB
However, H+ ions can be generated within the brain (on the other side of the BBB)
CO2 can move through the BBB
In the smooth muscle cells and neural tissue, CO2 and H2O in the presence of carbonic anhydrase leads to the formation of bicarbonate and H+
So this H+ that is produced acts as a vasodilator
See notes for diagram
How does NO cause vasodilation?
NO stimulates guanylyl cyclase which converts GTP to cGMP which then causes vasodilation
Arginine can generate NO to give citrulline
Describe the brain compartments?
See notes
Most of the neurones are surrounded by ECF
CSF is produced by specific cells that are associated with the ventricles (particularly the lateral ventricles) - CHOROID PLEXUS
CSF is produced from the blood - it doesn’t have the cells but even the constituents are not the same
The light blue circle - there are certain structures within the brain that receive blood flow like everywhere else in the brain but there is NO BBB - molecules pass across these regions much more easily
These areas are called CIRCUMVENTRICULAR ORGANS
Describe the production of CSF
Formed by the CHOROID PLEXUS. The choroid plexus is a plexus of cells that produces the cerebrospinal fluid in the ventricles of the brain. The choroid plexus consists of modified ependymal cells.
Capillaries surrounded by ependymal cells (tight junctions)
Ependymal cells secrete molecules into the ventricles to make the CSF - this is why the CSF is different to blood
Volume of CSF = 80 - 150 mL
Volume of CSF formed per day = 450 mL/day
What is the path of CSF?
Path of CSF:
- Lateral Ventricles
- 3rd Ventricle (via interventricular foramina)
- Cerebral Aqueduct
- 4th Ventricle
- Subarachnoid Space (via medial and lateral apertures)
