Neurology 5 - Blood brain barrier Flashcards
How long does cerebral blood flow need to be interrupted for unconsciousness to result?
4 seconds
Define syncope and list its causes
- Fainting due to temporarily reduced blood supply to the brain
- Caused by low blood pressure, postural changes, vaso-vagal shock, sudden pain, emotional shock
List the symptoms of hypoglycaemia
- Disorientation
- Slurred speech
- Impaired motor function
- Below 2mM results in unconsciousness, coma and death
What is cerebral blood flow regulated by?
- Mechanisms affecting total cerebral blood flow
- Mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow (chemical and neural regulation)
- Autoregulated between MAP 60-160mmHg
Describe the process of global autoregulation of cerebral blood flow
- 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.
What happens above and below the autoregulatory pressure range?
- Below there will be compromised brain function
- Above there will be swelling and increased intracranial pressure
Describe the pattern of vascularisation in the CNS tissues
- Arteries enter CNS tissue as branches of surface pial vessels
- These branches penetrate into the brain parenchyma
- They branch into capillaries, which drain to venules and veins
- The veins drain to surface pial veins
List the neural factors regulating cerebral blood flow
- Sympathetic nerve stimulation (vasoconstriction of large arteries)
- Parasympathetic facial nerve stimulation (vasodilation)
- Central cortical neurones (vasoconstrictor neurotransmiters released)
- Dopaminergic neurons (vasoconstriction related to increased brain activity, more localised)
Describe how dopaminergic neurones have local effect on cerebral blood flow
- Innervate penetrating arterioles and pericytes around capillaries
- May participate in diversion of blood to areas of high activity
- May cause contraction of pericytes via aminergic and serotinergic receptors
List the chemical factors that cause vasodilation in local autoregulation of CBF
- CO2
- pH
- Nitric oxide
- K+
- Adenosine
- Anoxia
Describe the formation of CSF
- Formed by the choroid plexus
- Leaky capillaries but local ependymal cells have extensive tight junctions
- CSF secreted into ventricles
Describe the pathway of CSF
- Lateral ventricles to 3rd ventricle via interventricular foramina
- Down cerebral aqueduct into 4th ventricle and into subarachnoid space via medial and lateral apertures
- It circulaties to eventually reach arachnoid granulations
What are the functions of CSF?
- Protection as it surrounds the brain
- Nutrition of neurones
- Transport of molecules
Compare the composition of plasma and CSF
- CSF has lower potassium, higher magnesium, lower calcium, higher chloride and lower bicarbonate ions
- CSF has lower amino acids
- CSF has a similar pH and osmolarity
Why is it clinically important that CSF has little protein?
If there is more protein in the CSF this can indicate a bacterial infection or damage to the blood-brain barrier
Why is the blood brain barrier important?
- Activity of neurones is highly sensitive to composition of local environment
- CNS needs to be protected from fluctuations in blood composition
Where are the capillaries of the blood brain barrier derived from?
Surface pial vessels - the branches get more like the blood brain barrier the deeper they get into the brain
List the differences between BBB capillaries and normal capillaries
- Many tight junctions and cell-cell contacts
- Little transport
- Dense pericyte coverage in BBB, to maintain capillary integrity and function
- Covered with the end feet of astrocytes which produce growth factors to induce blood-brain barrier qualities
What are circumventricular organs?
- Areas close to the ventricles where the capillaries lack BBB properties
- Capillaries are fenestrated, and the organs are involved in secretion or need to sample the plasma
- There is limited exchange between these vessels and the CSF, as ependymal lining cells are much tighter
Give examples of circumventricular organs
- Posterior pituitary
- Median eminence
- Area postrema (samples plasma for toxins to induce vomiting)
What is the clinical importance of the blood brain barrier?
- Breaks down in inflammation, infection, trauma and stroke
- Do you want a drug to cross the BBB and get to the brain or not?
- Antihistamine initially crossed the blood brain barrier and caused drowsiness, so now non-drowsy versions are available that cannot cross the blood brain barrier as they are polar
How does the BBB affect treatment of Parkinsons Disease?
- Raising dopamine levels is a therapy for parkinsons
- Dopamine cannot cross the blood brain barrier as it is very hydrophilic
- L-DOPA can cross the blood brain barrier, but it is often converted to dopamine peripherally (in the blood)
- It must therefore be co-administered with carbidopa, which blocks DOPA decarboxylase in the blood, so DOPA is not converted to dopamine. Carbidopa cannot cross the blood brain barrier
How does carbon dioxide cause cerebral arterial vasodilation?
- H+ can’t cross the blood brain barrier
- CO2 from neural metabolic activity is converted to hydrogen ions by carbonic anhydrase
- H+ can enter smooth muscle
- CO2 from the blood can be converted to hydrogen ions in the smooth muscle too
- Lower pH causes smooth muscle to relax
What are arachnoid granulations?
Openings in the arachnoid mater allowing circulation between the plasma and CSF
How can lipophilic and hydrophilic molecules cross the blood brain barrier?
- Lipophilic molecules by simple diffusion, such as oxygen, carbon dioxide and anaesthetics
- Hydrophilic substances need specific transport mechanisms (water via aquaporins, glucose via GLUT1, amino acids and electrolytes)
