5. Central Blood Flow and Regulation and BBB Flashcards
How much oxygen is supplied to the brain per minute?
55ml/100g
Brain weighs about 1400g
What happens when blood flow to the brain is reduced by more than 50%?
Insufficient oxygen delivery
Significantly impaired function
How long will disruption of CBF take for unconsciousness?
Just 4 seconds
A few minutes will lead to irreversible damage
Define syncope and list some causes
(fainting) a common manifestation of reduced blood supply to the brain Causes: LOW BP postural changes vaso-vagal attack sudden pain emotional shock
Why is there a vast surplus of glucose delivery to the brain?
Because the brain can only metabolise glucose, uses 50-60% of body’s glucose according to some studies
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
What is normal fasting glucose?
4-6mM
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 is local regulation?
Local brain activity determines the local oxygen and glucose demands therefore requires local changes in blood supply
Summarise pattern of CNS vascularistaion
Arteries enter the CNS tissue from as branches of the surface pial vessels. These branches penetrate into the brain parenchyma branching to form capillaries which drain into venules and veins which drain into surface pial veins.
What’s maximum distance a nuerone is from a capillary
No more than 100 uM
VERY DENSE VASCULARISATION
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)
Neuronal control of global brain blood flow not well defined, importance unknown
What feature do capillaries in the brain have that allow them to contract?
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
May participate in diversion of cerebral blood flow to areas of high activity.
Cause contraction via aminergic/sertoninergic receptors
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 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
This internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)
Describe how nitric oxide (NO) causes vasodilation.
Nitric oxide stimulates guanylyl cyclase
Guanylyl cyclase converts GTP cGMP
cGMP causes vasodilation
How do local changes allow mapping of the brain?
Changes to cerebral blood flow allow imaging techniques such as PET scanning and fMRI, increased blood flow = increased neuronal activity
Where is CSF produced?
Choroid plexus – these are specific cells associated with the ventricles (in particular the lateral ventricles)
Brain essentially floats in CSF protective function
What name is given to parts of the brain that receive blood flow like anywhere else but do not have a blood-brain barrier?
Circumventricular organs
Describe the passage of CSF through the ventricular system.
CSF is produced by specialized ependymal cells(often ciliated epithelial like glial 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
What is the volume of CSF in a normal person?
80-150ml
Contrast capillary and ependymal cells?
Capillaries are leaky however ependymal cells have tight junctions
What is the volume of CSF formed per day?
450ml
State three functions of the CSF.
Protection (chemical and physical)
Nutrient provision to neurons
Transport of molecules
Compare and contrast CSF and plasma
CSF has less potassium CSF has more magnesium CSF has less calcium CSF has fewer amino acids/protein CSF has less bicarbonate CSF has more chloride
Clinical significance of little CSF protein
Proteins/large molecules can’t cross the BBB, so if high then may be indicative of compromised BBB
Describe the structure of the blood-brain barrier. Which cells are involved?
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 running along the capillary wall
When the pericytes contract they make it more likely for the molecules to leave the capillary
Why does a BBB make sense?
because the activity of neurones is highly sensitive to the composition of local environment, and the CNS must be protected from the fluctuations in the composition of the blood
What level is BBB at?
Level of CNS capillaries
What type of molecule can cross the blood-brain barrier easily?
Lipophilic molecules
How do water and glucose cross the blood-brain barrier?
Water pass through aquaporin molecules
Glucose passes through Glut 1 transporters
Name three circumventricular organs(areas that lack BBB).
Median eminence region of the hypothalamus, posterior pituitary
Subfornical organ
Their capillaries are fenestrated, ependymal lining close to organs is tighter to limit exchange between them
Compare peripheral and BBB capillaries
BBB continuous with little transcellular vesicular transport, cardiac capillary has vesicular transport. Peripheral vessels have sparse pericytes, BBB dense.
BBB relationship to antihistamines and Parkinsons
H1 blockers were hydrophobic and could cross BBB, made people drowsy, used as sleep pills today, second generation blockers are polar so no BBB cross
Affects treatment of parkinsons as most of L-DOPA converted to dopamine peripherally less available to the brain, so CARBIDOPA (dopa decarboxylase inhibitor) given alongside so no conversion outside BBB and can’t enter BBB so ensures increased dopamine in brain
Osmolarity of CSF and plasma?
The same
