Central Blood Flow Regulation and the Blood-Brain Barrier Flashcards
Blood glucose below what value will lead to loss of consciousness, coma and death?
2 mM
On what levels can you regulate 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
How is TOTAL cerebral supply blood supply regulated
Autoregulation. This involves the myogenic mechanism (VSMC)- stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP. This alters radius and hence flow.
What are the two types of control of LOCAL cerebral blood flow regulation?
Neural and Chemical
What are the four factors that affect neural control of cerebral blood flow?
Sympathetic innervation of the main cerebral arteries – causes vasoconstriction when arterial blood pressure is high to reduce the blood flow
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 (adrenaline/NA) that cause vasoconstriction
Dopaminergic neurons – release dopamine and cause 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?
What is the purpose of the dopamingergic neurones doing this?
Pericytes around capillaries and penetrating arterioles
Pericytes are contractile cells and dopamine can make them contract and hence make the capillaries contract
Dopaminergic neurons use these mechanisms to divert blood flow to areas in brain that are more active
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)
these factors are generally localised and they are all vasodilators
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 how nitric oxide (NO) causes vasodilation.
Nitric oxide stimulates guanylyl cyclase Guanylyl cyclase converts GTP - cGMP cGMP causes vasodilation
Where is CSF produced?
Choroid plexus – these are a specific plexus cells associated with the ventricles (in particular the lateral ventricles)
What name is given to parts of the brain that receive blood flowlike anywhere else but do not have a blood-brain barrier?
Circumventricular organs - contain fenesterated capillaries. They generally need this due to their function of secreting into the plasma OR sampling the plasma
Examples include subfonical organ, OVLT (Y1 enteroendocrine)
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
What is the volume of CSF in a normal person?
80-150 mL
State three functions of the CSF.
Protection (chemical and physical)
Nutrient provision to neurons
Transport of molecules
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.
Median eminence region of the hypothalamus
Subfornical organ
Organum vasculosum of the lamina terminalis (OVLT)
Neurohypophysis
State four components that have a lower concentration in the CSF than the plasma.
K+ Calcium Amino acids Bicarbonate
What may protein in the CSF indicate
State two components that have a higher concentration in the CSF than the plasma.
May indicate breach/damage
Magnesium and Chloride ions
How is the osmolarity different between the CSF and the plasma?
The same
How is the pH different in the CSF compared to the plasma?
CSF is slightly more acidic
How do Vessel BBB properties differ in deeper vessels.
Vessel BBB properties increased in deeper vessels.
bbb at level of?
CNS capillaries
CVO- Circumventricular organs - ventricular ependymal lining
•The ventricular ependymal lining close to these areas can be much tighter than in other areas, limiting the exchange between them and the CSF.
Why do Circumventricular organs need access to the blood
- the posterior pituitary and median eminence secrete hormones
- the area postrema samples the plasma for toxins and will induce vomiting
- others are involved in sensing electrolytes and regulate water intake.
BBB- capillaires of CNS parenchyma are dervied from
surface pial vessesl
BBB capillaries have tight junctions
at endothelial cell-cell contacts
2 differences between peripheral and BBB capillaries
Blood brain barrier:
High dense pericyte coverage
Covered in end feet from astrocytes
Treatment for parkinons: Dopamine can’t get past BBB so use what?
What is the issue with this
Solution
L-DOPA
Converted peripherally into dopamine
Coupled with Carbidopa- DOPA decarboxylase inhibitor
- the inhibitor can’t cross the blood brain barrier so doesn’t affect the dopamine production.
