5 Flashcards
How much of the cardiac output does the brain receive?
15%
What happens when blood flow to the brain is reduced by more than 50%?
insufficient oxygen deliver and the brain function becomes significantly impaired
What is the most common manifestation of reducing blood supply to the brain?
syncope (fainting)
State some causes of syncope
low BP postural changes vaso-vagal attack sudden pain emotional shock
What is the principal source of energy to the brain and what happens if there is a shortage?
glucose
ketones can also be metabolised
NOTE: glucose cannot be stored in the brain, so the brain needs a constant rich blood supply
Name the 2 mechanisms by which cerebral blood flow is maintained
- mechanisms affecting total cerebral blood flow
- mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow - blood is diverted to parts of the brain that need it at a certain time
Between which MABP is cerebral blood flow auto-regulated?
between approx. 60 and 160 mmHg
Describe how cerebral blood flow is regulated between 60 and 160 mmHg?
Give an example by describing what happens as a result of an increase in BP
MYOGENIC RESPONSE (to stretch of blood vessel walls)
- The smooth muscle lining arteries can stretch in response to blood flow
- Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP
- An increase in pressure on the vessel wall -> myogenic response -> contraction -> decreases CBF
What happens when the blood pressure decreases below the auto-regulatory pressure range (approx. 60 and 160 mmHg)?
compromised brain function
What happens when the blood pressure increases above the auto-regulatory pressure range (approx. 60 and 160 mmHg)?
intracranial pressure increases
What are the branches controlling local auto-regulation?
Neural Control and Chemical Control
Arteries enter the CNS tissue from branches of the ______ vessels.
Describe what they are and their circulation
pial
The pial vessels are intracranial vessels on the surface of the brain within the pia–arachnoid
The branches penetrate into the brain parenchyma branching to form capillaries which drain into venules which drain into surface pial veins
List the neural factors that play a role in local auto-regulation of cerebral blood flow
- Sympathetic nerve stimulation to main cerebral arteries, producing vasoconstriction
- Parasympathetic (facial nerve) stimulation – facial nerve fibres are innervated by parasympathetic fibres -> slight vasodilation
- Central cortical neurones – neurones within the brain release vasoconstrictor neurotransmitters, such as catecholamines -> vasoconstriction
- Dopaminergic neurones producing vasoconstriction (localised effect related to increased brain activity)
Summarise the action of dopaminergic neurones in producing local vasoconstriction (particularly in capillaries)
- Brain capillaries have pericytes wrapping around them – these pericytes are contractile
- Dopaminergic neurones innervate SM around arterioles and pericytes around capillaries
- Activation = contraction of pericytes
- This decreases local blood flow -> diverts blood to more active areas
Describe the general mechanism off action of chemical control of blood flow
- When cells are active they produce lactic acid
- The H+ ions in the lactic acid cause a drop in pH -> local vasodilation
• K+ is released at one stage of the action potential and acts as a vasodilator
Describe the mechanism by which CO2 can regulate localised cerebral blood flow
- H+ ions DO NOT cross the BBB, but they can be generated within the brain, on the other side of the BBB
- CO2 (from blood/local metabolic activity) can move through the BBB
- CO2 + H2O —(carbonic anhydrase)–> bicarbonate + H+ in surrounding neural tissue and smooth muscle cells
- Elevated H+ -> decreased pH -> relaxation of contractile smooth muscle -> increased flow (vasodilator)
How can local changes to cerebral blood flow be imaged?
PET scanning and functional MRI
Where is CSF produced?
by regions of choroid plexus in the (walls of) cerebral ventricles
What lines the ventricular system?
The ventricles, aqueducts and canals of the brain are lined with ependymal cells (epithelial-like glial cells, often ciliated).
In some regions of the ventricles (where CSF is produced), this lining is modified to form the choroid plexus
Describe the formation of CSF
(CSF formed by choroid plexus)
• Capillaries are surrounded by ependymal cells
• Capillaries are leaky, but adjacent ependymal cells have extensive tight junctions
• Ependymal cells secrete molecules into the ventricles to make CSF
Describe the path of CSF
- lateral ventricles
- > 3rd ventricle via interventricular foramina
- > down cerebral aqueduct into 4th ventricle
- > subarachnoid space via medial and lateral apertures
- > circulates
- > (excreted through kidneys or liver)
State the functions of CSF
protection (physical and chemical)
nutrition of neurones
transport of molecules
Describe the differences in composition of the CSF to blood plasma
LOWER in the CSF: - K+ - Calcium - Amino Acids - Bicarbonate HIGHER in the CSF: - Magnesium - Chloride
OSMOLARITY IS THE SAME.
pH of the CSF is slightly more ACIDIC
REMEMBER: CSF has very little protein
What does an increase in proteins in the CSF indicate?
infection or tissue damage
normally: CSF has very little protein
What is the function of the BBB
to protect the CNS from fluctuations in the composition of the blood (The activity of neurones is highly sensitive to the composition of local environment):
- protects the brain tissue from certain toxins and circulating transmitters like catecholamines
- also protects the brain from wide variations in ion concentrations
Describe the structure of the BBB
- Endothelial cells lining capillaries in the brain have VERY TIGHT JUNCTIONS (non-fenestrated)
- This is so that a lot of molecules can’t pass readily through the BBB
- The capillaries are also surrounded by pericytes - when they contract, they make it more likely for molecules to escape the capillary
OVERALL: it’s mainly the tight junctions between endothelial cells forming the BBB but also pericytes
Describe how the capillary pericyte coverage differs in different area of the brain
Peripheral vessels have sparse pericyte coverage, while BBB capillaries have dense pericyte coverage.
(as they penetrate into the brain, their phenotype changes to form much tighter barriers)
BBB capillaries are also covered in “end-feet” from astrocytes - important for maintaining BBB properties.
What is meant by BBB capillary ‘tightness’?
Solutes that exchange across peripheral capillaries can’t cross the BBB
- This applies mainly to hydrophilic solutes (glucose, amino acids, many antibiotics, some toxins etc.)
- the exchange of these substances occurs using specific membrane (influx and efflux) transporters
NOTE: Lipophilic molecules cross the BBB via diffusion
What are CVOs?
What are they involved in?
Give some examples
circumventricular organs - areas of the brain lacking BBB properties
- found close to ventricles
- Their capillaries are fenestrated (leaky) - lie OUTSIDE of the BBB
- These regions of the brain are involved in secreting into the circulation, or sampling the plasma
- e.g. median eminence, subfornical organ and organum vasculosum of the lamina terminalis
Describe and explain the lining of the ventricle close to CVOs (circumventricular organs)
- The ventricular ependymal lining close to these areas can be much tighter than in other areas
- This limits the exchange between them and the CSF
Whta is the CLINICAL IMPORTANCE OF THE BBB?
• The BBB breaks down in many pathological states: inflammation, infection, trauma, stroke
• A major issue in pharmacology:
—–> Many therapeutic drugs cannot access the brain
—–> Others may access the brain too readily causing adverse effects
Describe the difference in older and second generation antihistamines, and why the BBB plays a role in this
- “old-fashioned” H1 blockers are hydrophobic and can cross the BBB (histamine is important in wakefulness)
so these antihistamines made people drowsy - Second-generation antihistamines are polar, therefore don’t readily cross the BBB —> no drowsiness
Describe how the BBB affects the treatment of PARKINSON’S DISEASE
A key therapy in Parkinson’s disease is pharmacologically raising the levels of dopamine in the brain
• dopamine cannot cross the BBB (so peripheral administration doesn’t work)
• L-DOPA can cross the BBB via an amino acid transporter, and is converted to dopamine in the brain
• BUT circulating L-DOPA is also converted to Dopamine peripherally, so little is available to access the brain
Answer: Co-administration with the DOPA decarboxylase inhibitor, Carbidopa
(Carbidopa cannot cross the BBB, so does not affect conversion of L-DOPA in the brain)
