Neuro 5: Regulation of blood flow (BBB) Flashcards
T/F: the brain has highest o2 consumption in body
False- kidney is higher. brain 3 ml 02/min per 100g , kidney 5ml o2/min per 100g
What is the blood flow to the brain not o2 but blood flow
55ml/100g tissue/minute
What % is the brain of: body weight, cardiac output, o2 consumption
Weight: 2%, CO: 15%, o2 consumption: 20%
Conseuquences of blood flow being reduced by more than 50%
Insufficient o2 delivery and impaired function
t/f 10 seconds of Cerebral Blood Flow (CBF) interruption will result in unconsciousness
t: in fact, it only takes 4 seconds of interrupted CBF f ro unconsciousness, and after a few minutes tissue damange
What is syncope and what are the causes
Fainting due to inadequate CBF
Low BP, postural changes, vaso-vagal attack, sudden pain, emotional shock. All result in temporary reduction of CBF.
What % of body’s glucose does brain use
60%
Why is glucose vital to brain
It can’t store or sythesise or utilise any other energy source except ketone bodies in starvation
Signs of hypoglycaemia
Disorietation, slurred speech and impaired motor function
What is dangerously low glucose level
Below 2mM can cause unconsciousness, coma and death. Normal fasting levels are 4mM-6mM
Overall, how is cerebral blood flow regulated
By:
Mechanisms affecting TOTAL cerebral flow
Mechanisms relating activity to the requirement in specific brain regions by altering LOCALISED blood flow
You need to maintain so the blood has access to glucose and o2
How is total cerebral flow regulated (one of the two factors affecting CBF)
What is the effect of not enough overall blood flow to the brain
What is the effect of too much overall blood flow to the brain
AUTOREGULATION between MABP 60 and 160mmHg.
Stretch sensitive cerebral vascular smooth muscle:
- CONTRACTS at high BP (to reduce flow)
- RELAXES at low BP (to increase flow)
- Note… this is not to control BP…. this is to allow blood to the brain….. so it’s the opposite of what is useful to control BP*
Below the autoregulatory range –>compromised function
Above the autoregulatory range –> increased flow, swelling of brain tissue, increased intracranial pressure
How is local blood flow regulated- give the 2 mechanisms (one of the two factors affecting CBF)
Local brain activity determines o2 and glucose demands, local changes required –> LOCAL AUTOREGULATION.
- Neural control
- Chemical control
Pattern of vascularisation within CNS tissue
Arteries or arterioles (bit unclear) enter CNS tissue from branches of SURFACE pial vessels.
The branches penetratrate into brain parenchyma, branch to form capillaries, drain into venules and veins which drain into surface pial veins
Outline how neural factors impact cerebral blood flow (this is mostly local)
- Sympathetics constrict MAIN cerebral arteries when arterial BP high
- Parasympathetic facial nerve produce slight vasodilation
- Central cortical neurones release vasoconstrictor neurotransmitters like the catecholamines.
* 4. Dopaminergic neurones producing vasoconstriction- localised effect related to increased braina activity
Outline local regulation of CBF by dopaminergic neurons
Innervate penetrating arterioles and PERICYTES , divert cerebral blood to high activity areas, causes contraction of pericytes via AMINERGIC and SERETONINERGIC receptors
What are the functions of pericytes
Cells that wrap around capillaries- have immune, transport and contractile function (TIC)
Outline chemical regulation of local CBF
CO2 (indirect), increased H+ or lactic acid or other acids, NO, K+, adenosie, anoxia all VASODILATE.
Kinins, prostaglandins, histamine and endothelins also have an effect
How does CO2 increase local CBF?
NOT DIRECTLY
It passes from the blood across the endothelium into the VSM, or from brain tissue around the vessel into the VSM.
Then converted by carbonic anhydrase, with water into H+ and HCO3-.
High H+ means decreased pH which relaxes the contractile smooth muscle cells and increases blood flow.
KEY: CO2 is dervied from neural metabolic activity
T/F: H+ ions within the blood vessel will stimulate relaxation as it indicates increased neural metabolic activity
FALSE! H+ within the blood vessel cannot pass through the endothelium into the smooth muscle to cause relaxation. However, H+ from neural tissue surrounding the vessel (formed from CO2 and H2O and carbonic anhydrase) can go to smooth muscle and cause relaxation
How are local changes to CBF useful
Can look at the changes in imaging and map brain activity using PET and MRI
State the fluid types in the brain
Blood, CSF and ECF
Where is CSF produced
Choroid plexus lining ventricles.
What is choroid plexus
Ependymal cells line all the aqueducts and ventricles, in some parts of the ventricles, the lining is modified to form branched VILLUS structures= choroid plexus
T/f: Ependymal cells often ciliated
T
How is CSF formed
Leaky capillaries, but not all of what leaks out of the capillary becomes the CSF- there are very tight junctions on the EPENDYMAL cells, so they don’t let everything pass from the blood into the ventricles
State the path of CSF
secreted into lateral ventricles
then, via the interventricular foramina (i.e. a channel from each lateral ventrical to the 3rd ventricle), to the 3rd ventricle,
then via the cerebral aqueduct to the 4th ventricle, then into the subarachnoid space via medial and lateral apertures
Volume of CSF
80-150ml
Function of CSF
Protection, nutrition of neurons and transport of molecules
Difference in composition in CSF vs plasma
In CSF: Less K+, more Mg+, LESS PROTEIN but same osmolarity
pH slightly lower more acidic
CSF has little protein- why is it clinically imprtant
Increased proteins indicates infection (antibodies)
How did we find about BBB
When we injected dye it accumulated in most tissues apart from brain and retina
Why is BBB needed
Neuronal activity sensitive to the composition of local environment, so CNS needs to be protected from fluctuations in blood composition
At what level is the BBB
Level of CNS capillaries
Differentiate fenestrated and sinusoid capillaries
Fenestrated- holes but in tact BM
Sinusoids- large spaces betwen cells (intercellular gaps) and incomplete basement membrane
What exactly is the BBB
BBB is the extensive tight junctions between endothelial cell-cell contacts in the penetrating branches of surface pial vessels, reducing solute and fluid leak across capillary wall
Think about those penetrating arterioles branching from pial vessels:
The surface pial vessels are permeable to most small molecules but have reduced passage of proteins across from blood to the neural tissue
In the branches which penetrate, there is drastically reduced passage of cellular elements and it’s impermeable to most hydrophilic molecules.
Further down the penetrating branches, there is negligible permeability, polarized phenotype and this is the site of active drug exclusion
T/F: there is little transcellular and paracellular transport across BBB
T- little vesicular transport as well. Continuous type capillary
Aside from the endothelial tight junctions, state other differences between peripheral and BBB capillaries
BBB covered with pericytes, peripheral capillaries have sparse pericytes
BBB capillaries covered with end-feet from astrocytes
Which solutes are excluded by the BBB
In particular, hydrophilic ones.
e.g. glucose, AAs, many antibiotics, many toxins
How does BBB control exchange of hydrohilic substances
SPECIFIC MEMBRANE TRANSPORTERS- influx and efflux transporters
Why is meninges more commonly affected by blood borne infections. Counterintuitively, why could loss of BBB help with clearing infection
Meningeal vessels do not contain the BBB
Breakdown of BBB can allow immune cell access
How does BBB deal with lipophilic molecules
it doesn’t, really….. o2, co2, alcohol and anaesthetics cross BBB. Access or removal via diffusion down conc. gradient
How do the following substances enter the BBB
Water
Glucose
AA
Electrolytes
Water- aquaporin AQP1 and AQP4
Glucose- GLUT1
AA- 3 different transporters
Electrolytes by specific transporter systems
What are the circumventricular organs
Areas close to ventricles which have FENESTRATED capillaries.
The ependymal cells lining the ventricles are even tighter here than in rest of brain to stop movement of fluid from the leaky capillaries into the CSF
Why do CVOs exist
They are invoved in secreting into the circulation or need to sample plasma (e.g. pituitary gland and median eminence secrete hormones, or the area postrema samples plasma for toxins and induces vomiting), other areas involved in sensing electrolytes and water intake
- post pit
- median eminence
- area postrema
- other areas involved in electrolyte balance
When can BBB breakdown occur
Strokes, inflammation, trauma, infection
New vs old antihistamines and BBB
Old ones were hydrophobic, cross BBB and cause drowsiness (as histamine important in alertness and wakefulness) , these are now used for over counter sedatives
New ones are hydrophilic
How does BBB affect treatment of Parkinson’s
Because you want to give dopamine, but dopamine doesn’t cross BBB
So you could give L-DOPA, which does cross the BBB, but if you do most will be converted to dopamine in the blood by DOPA decarboxylase
So you give them L-DOPA with a DOPA decarboxylase inhibitor called Carbidopa…. and the inhibitor is designed not to pass through the BBB so it stops conversion inthe blood (allowing L-DOPA to enter brain) but not in the brain! C
