Blood Brain Barrier Flashcards
Describe the blood flow to the brain
Blood flow to the brain: high at approx. 55ml/100g tissue/min
(~15% of cardiac output, while only ~2% of body weight and 20% O2 consumption)
Compare the oxygen consumption of the brain to that of other tissues
Brain- 3mlO2/min per 100g Kidney- 5 Skin- 0.2 Resting Muscle- 1 Contracting muscle- 50
Describe the consequences of reduced blood flow to the brain
Whenever blood flow to the brain reduced by more than 50% insufficient oxygen delivery function becomes significantly impaired
If total CBF is interrupted for as little as 4 seconds, unconsciousness will result
After a few minutes irreversible damage occurs to brain
Summarise syncope (fainting)
Syncope (= fainting) is a common manifestation of reduced blood supply to the brain.
Bleeding and loss of blood is a cause
Has many causes including low blood pressure, postural changes, vaso-vagal attack, sudden pain, emotional shock etc.
All result in a temporary interruption or reduction of blood flow to the brain.
Describe a vaso-vagal attack
Vasovagal syncope (vay-zoh-VAY-gul SING-kuh-pee) occurs when you faint because your body overreacts to certain triggers, such as the sight of blood or extreme emotional distress. It may also be called neurocardiogenic syncope. The vasovagal syncope trigger causes your heart rate and blood pressure to drop suddenly. Blood pools in the legs and extremities whilst going to the brain
Summarise the glucose supply to the brain
Normally, vast surplus provision of glucose (the principal energy source) to the brain via the blood.
Some estimates suggest that the brain uses 50-60% of the body’s glucose!
This supply of glucose vital because the brain cannot store, synthesize or utilise any other source of energy (although, in starvation, ketones can be metabolised to a limited extent – adaptation possible in chronic undernutrition?)
- 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
Describe the consequences of hypoglycaemia on brain function
Many of us might have witnessed or experienced the effects of reduced glucose delivery to the brain in insulin-dependent diabetic individuals, where blood sugar levels drop- administering too much insulin- or not eating enough glucose
An individual appears disoriented, slurred speech, impaired motor function.
Doesn’t just happen to diabetics- anyone with hypoglycaemia will start to feel wobbly and lethargic
If the glucose concentration falls below 2mM it can result in unconsciousness, coma and ultimately death. (Normal fasting levels 4-6 mM)
What is the brain
One of the most metabolically demanding and vascularised tissues
Describe the importance of the maintenance of cerebral blood flow
Because of the constant need by the brain for oxygen and glucose
it is vital that the cerebral blood flow be maintained
which means that an efficient regulatory system must be operational.
The brain is vulnerable to interruptions in its blood supply because it can store neither oxygen nor glucose, and cannot normally undergo anaerobic metabolism.
Cranial blood vessels are controlled by autoregulation to maintain a constant blood supply.
Describe the metabolic adaptations of the CNS to starvation
Under conditions of starvation for several days, the central nervous system can adapt to use ketones (fat derivatives acetoacetate and hydroxybutyrate) as its main energy source. These compounds normally make up approximately 30% of the fuel for the brain in adults but, after fasting for 40 days, this can rise to 70%.
- On what levels do you get regulation of cerebral blood flow?
mechanisms affecting total cerebral blood flow- concerning the cerebral arteries supplying the brain tissue
mechanisms which relate activity to the 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?
Total cerebral blood flow IS AUTOREGULATED
between mean arterial blood pressures (MABP) of approximately 60 and 160 mm Hg
Explain how this auto regulation is achieved
Over a wide range of arterial pressures, the arteries and arterioles dilate or contract to maintain blood flow.
Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP.
Contracts to reduce blood flow
Relaxes to increase blood flow- to compensate for the reduced BP
Compare the consequences of reduced and increased MABP in the brain
Below this autoregulatory pressure range, insufficient supply leads to compromised brain function (as already discussed).- light-headed
Above this autoregulatory pressure range, increased flow can lead to swelling of brain tissue which is not accommodated by the “closed” cranium, therefore intracranial pressure increases – dangerous.
Can’t increase volume as the space is closed- therefore the pressure must increase- putting pressure on structures in the brain.
Summarise local auto regulation
The local brain activity determines the local O2 and glucose demands, therefore local changes in blood supply required:
Local autoregulation
- 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 controls of the local regulation of cerebral blood flow
neural control- in response to various stimuli
chemical control- in response to physiology
Describe the pattern of vascularisation in CNS tissues
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.
The veins coalesce and return to the surface
Describe how densely the CNS is vascularised
No neurone more than 100µm from a capillary.
Inject liquid resin into brain vessels- will form a plastic cast- digesting away the parenchyma- leaving behind only the vessels- which show how densely vascularised the CNS is on a scanning EM
What are the four types of neural control of 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)- localised effect relating to brain activity.
What is important to remember about the neural control of global blood flow to the brain
The neural control on global brain blood flow is not well defined, and its importance is uncertain.
Chemical control- probably more important
Describe the local effect of dopaminergic neurones on CBF
Innervate penetrating arterioles and pericytes around capillaries
Pericytes are cells that wrap around capillaries; have diverse activities (e.g. immune function, transport properties, contractile)
may participate in the diversion of cerebral blood to areas of high activity - by contracting and reducing the blood flow to other areas
Dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors
- Name some chemical factors that increase blood flow to particular tissues.
Carbon dioxide (indirect) NO pH (H+, lactic acid, etc, direct) Anoxia Adenosine K+ Other (e.g. kinins, prostaglandins, histamine, endothelins)- both natural and synthetic factors
All increase blood flow by causing vasodilation
What is the normal pCO2 and blood flow to the brain
40kPa
1.0
As the partial pressure of pCO2 increases in the brain- so does the blood flow- see graph
What may the contractile cells be
Smooth muscle
Pericytes (in smaller vessels and capillaries)
Are H+ and CO2 able to cross the BBB
H+ can’t- therefore can’t cross from plasma to the vascular smooth muscle
CO2 can- therefore can cross from plasma to the vascular smooth muscle
- 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)
Summarise the cerebral arterial vasodilation by CO2
CO2 from the blood or from local metabolic activity generates H+ using carbonic anhydrase in surrounding neural tissue and in the smooth muscle cells.
Elevated H+ means decreased pH. This causes relaxation of the contractile smooth muscle cells, dilation of vessels, resulting in increased blood flow.
Describe how the local changes to blood flow allow imaging of the brain
Local changes to cerebral blood flow allow imaging and mapping of brain activity using techniques such as PET scanning and functional MRI (fMRI).
In the CNS, increased blood flow equates to increased neuronal activity.
Can see this on the brain as a result of increased H+ ions
- Describe how nitric oxide (NO) causes vasodilation.
Nitric oxide stimulates guanylyl cyclase
Guanylyl cyclase converts GTP cGMP
cGMP causes vasodilation
Summarise the fluid compartments of the brain
The brain is essentially “floating” in cerebrospinal fluid produced by regions of choroid plexus in the cerebral ventricles.
This is an important protective mechanism.
brain also bathed in its own tissue fluid- with fluid moving in and out of the I.C fluid
Where is CSF found
In the ventricular system and within the spinal canal
Describe the arachnoid granulations
Where CSF can lead the ventricular system
Openings between ventricular system and plasma on the outer surface of the brain and vessels in the arachnoid mater
Arachnoid granulations (also arachnoid villi, and pacchionian granulations or bodies) are small protrusions of the arachnoid mater (the thin second layer covering the brain) into the outer membrane of the dura mater (the thick outer layer). They protrude into the dural venous sinuses of the brain, and allow cerebrospinal fluid (CSF) to exit the subarachnoid space and enter the blood stream.
The largest granulations lie along the superior sagittal sinus, a large venous space running from front to back along the center of the head (on the inside of the skull). They are, however, present along other dural sinuses as well.
