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)- cause contraction of pericytes
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
Dopaminergic neurons cause contraction of pericytes via which receptors?
Aminergic and serotoninergic neurons - cause contraction of pericytes
Which fibres innervate the main arteries in the brain?
Sympathetic fibres
Name some chemical factors that increase blood flow to particular tissues. via vasodilaton
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 (VSMC’s relax)
high pH can be caused by ^CO2 as its converted to HCO3 and H+
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 –> lower pH 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 specific 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 eg posterior pituitary
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–>CSF flows down the cerebral aqueduct to the 4th ventricle—> enters the subarachnoid space (via medial and lateral apertures)—>eventually drains back into the venous system via arachnoid granulation
What is the volume of CSF in a normal person?
80-150 mL
What is the volume of CSF formed per day?
450 mL/day
State three functions of the CSF.
Protection (chemical and physical) Nutrient provision to neurons Transport of molecules
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
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 -secretes hormones posterior pituitary -secretes hormones Area Postrema samples the plasma for toxins and will induce vomiting. The leaky, fenestrated CVO vessels are required for these functions
State four components that have a lower concentration in the CSF than the plasma.
K+ Calcium Amino acids Bicarbonate
State two components that have a higher concentration in the CSF than the plasma.
Magnesium Chloride
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 has the treatment of parkinson’s been modified because of the BBB
Dopamine cannot cross BBB, but L-DOPA can, however L-DOPA is broken down (–>dopamine) peripherally by DOPA decarboxylase So co-administering a DOPA decarboxylase inhibitor that cannot cross BBB, so L-DOPA can be broken down in brain to exert its effect
