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
Brain can’t store, synthesise or utilise any other source
(Ketone bodies can be metabolized if there is a shortage)
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 CBF
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 smooth muscle surrounding arterioles is stretched, it will contract to maintain a constant blood flow
Occurs when there is a change in BP in the body
What are the 2 types of control of cerebral blood flow regulation?
Neural
Chemical
What are the 4 types of neural control of cerebral blood flow?
Sympathetic innervation of the main cerebral arteries: causes vasoconstriction when arterial BP is high
Parasympathetic (facial nerve) stimulation: can cause slight vasodilation
Central cortical neurons: release vasoconstrictor neurotransmitters e.g. catecholamines (A + NA)
Dopaminergic neurons: produce vasoconstriction (localised effect related to increased brain activity)
What feature do capillaries in the brain have that allow them to contract?
Surrounded by pericytes:
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 + smooth muscle around arterioles
Dopaminergic neurons cause contraction of pericytes via which receptors?
Aminergic + serotoninergic neurons
Name 7 chemical factors that increase blood flow to particular tissues.
CO2 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, resulting in increased blood flow
Describe how carbon dioxide indirectly causes vasodilation in the cerebral vessels.
H+ ions can’t cross the BBB, but CO2 can
CO2 moves from the blood through the BBB into the smooth muscle cells
Within the smooth muscle cells, in the presence of carbonic anhydrase, CO2 reacts with water to form bicarbonate + H+ ions
Internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)
Where is CSF produced?
Choroid plexus: specific cells associated with the ventricles (particularly the lateral ventricles)
What name is given to parts of the brain that receive blood flow like anywhere else but do NOT have a BBB?
Circumventricular organs
Describe the passage of CSF through the ventricular system.
CSF produced by specialized ependymal cells of the choroid plexus (mainly in lateral ventricles)
From lateral ventricles, goes through interventricular foramina to 3rd ventricle
Then flows down the cerebral aqueduct to 4th ventricle
Enters subarachnoid space (via medial + lateral apertures)
Drains back into venous system via arachnoid granulations
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 3 functions of the CSF.
Protection (chemical + physical)
Nutrient provision to neurons
Transport of molecules
Describe the structure of the blood-brain barrier. Which cells are involved?
Capillaries in the brain have endothelial cells with very tight junctions so there is tight control of what can pass through the walls
Capillaries are also surrounded by pericytes with end-feet of astrocytes running along the capillary wall
What type of molecule can cross the blood-brain barrier easily?
Lipophilic molecules
How do water and glucose cross the blood-brain barrier?
Water: aquaporin channels
Glucose: GLUT-1 transporters
Name 3 circumventricular organs.
Median eminence region of the hypothalamus
Subfornical organ
Organum vasculosum of the lamina terminalis
State 4 components that have a lower concentration in the CSF than the plasma.
K+
Ca2+
Amino acids
Bicarbonate
State 2 components that have a higher concentration in the CSF than the plasma.
Mg2+
Cl-
How is the osmolarity different between the CSF and the plasma?
Osmolarity is the same
How is the pH different in the CSF compared to the plasma?
CSF is slightly more acidic
What happens if cerebral blood flow is interrupted for a) 4 seconds, b) few minutes?
4 seconds: Unconsciousness
Minutes: Irreversible damage
What is syncope? What is it a common result of? List 4 common causes
Fainting
Results from reduced blood supply to brain
Low BP, Postural changes, Vaso-Vagal attack, Sudden pain
What happens if BP rises above the auto regulatory pressure range?
Increased flow can lead to swelling of brain tissue which isn’t accommodated by the “closed” cranium
Intracranial pressure rises
Describe the pattern of vascularisation in CNS tissues
Arteries enter CNS tissue as branches of surface Pial vessels
Branches penetrate into brain parenchyma to form capillaries which drain into venues + veins into surface pial veins
What does high protein content in CSF suggest?
Infection
Damage allowing plasma protein to enter CSF
How does the BBB protect the brain from infection?
Hydrophilic solutes can’t cross the BBB.
Blood borne infectious agents may have reduced entry into CNS tissue
Describe the capillaries in circumventricular organs. What is the function of these regions?
Fenestrated (leaky)
Sample composition of plasma/ secretion into circulation
Why are 1st generation antihistamines no longer used? What has replaced them?
They were hydrophobic, so could cross the BBB- made people drowsy.
Now we use polar drugs that can’t cross the BBB
How do we raise the levels of dopamine in the brain in Parkinson’s disease, when dopa decarboxylase converts L-DOPA in peripheral tissues?
Co-administer L-DOPA with Carbidopa (DOPA decarboxylase inhibitor which cannot cross the BBB)
Thus L-DOPA can be converted to dopamine in the brain
