Cerebral Blood Flow Regulation Flashcards
When does unconsciousness occur and irreversible damage?
If CBF interrupted for 4secs = unconsciousness
Few minutes = irreversible damage
Syncope?
Fainting
Common manifestation of reduced BS to the brain
Main principle energy source for the brain?
Glucose
[glucose] concentrations and impact?
Normal fasting levels = 4-6mM
If <2mM = unconsciousness, coma and death
How is CBF regulated?
x mechanisms affecting TOTAL CBF
x mechanisms with alter LOCALISED BF depending on activity
Auto-regulation range for CBF?
MABP 60-160mmHg
How is the CBF autoregulated to maintain the MABP?
Stretch-sensitive cerebral vascular SM
High BP - contracts
Low BP - relax
What can happen to the brain if the BP is too high?
Swelling of brain tissue as ‘closed’ cranium = intracranial pressure increases
What is local regulation mediated by?
Neural control
AND
Chemical control
How can local changes to CBF be measured?
Imaged on PET scans & fMRIs
Explain the vascularisation of the CNS
Arteries from the pia mater penetrate into the brain parenchyma –> form capillaries
These brain into veins/venules –> into the surface pial vessels
Relationship betw. neurone and capillary in the CNS
No neurone is >100um (micro) from a capillary
4 neural factors affecting CBF regulation?
- SN nerve stimulation
- PSN (facial nerve) stimulation
- Central cortical neurones
- Dopaminergic neurones
SN nerve stimulation (neural factor)?
To main cerebral arteries
VasoCONSTRICTION when MABP is high
PSN facial nerve stimulation (neural factor)?
Produces sligh vasoDILATION
Central cortical neurones (neural factor)?
Releases various vasoCONSTRICTOR NTs
e.g. catecholamines (A & NA)
Dopaminergic neurones (neural factor)?
LOCALISED vasoCONSTRICTION
Explain what dopaminergic neurones innervate
Innervate
x penetrating arterioles
x pericytes around capillaries
Explain how dopaminergic neurones function
May participate in the diversion of CBS to areas of high activity
Dopamine may cause contraction of pericytes via. aminergic & serotoninergic receptors
Pericytes?
Brain macrophages that wrap around capillaries - maintaining integrity & function
Diverse activity inc. immune function, transport property, contractile
Chemical factors affecting CBF?
Generally localised
CO2 (indirect) pH NO K+ Adenosine, anoxia, prostaglandins
Effect of pCO2 on CBF?
An increase in pCO2 = BF increases
Effect of CO2 on cerebral arteries?
VasoDILATION
Increase in H+ = decreases pH inside VSMCs = cell relaxes = vessels dilate = INCREASED BF
Where can the H+ (in chemical factors) be derived from?
Higher CO2 in blood (NOT directly from H+ in blood)
Increased neural metabolic activity
What produces CSF?
Choroid plexus (in the cerebral ventricles)
Choroid plexus?
Modifies ependymal cells that normally line the ventricles, aqueducts and canals of the brain
Capillaries of the choroid plexus vs. local ependymal cells?
Leaky vs. extensive tight junctions
Path of CSF?
- Lateral ventricles
- 3rd ventricle via. interventricular foramina
- Central aqueduct
- 4th ventricle
- Subarachnoid space via. medial & lateral apertures
LEAVES via. arachnoid granulations into superior saggital sinus
Volume of CSF?
80-150ml
Function of CSF?
Protection
Nutrition
Transport
What is similar in the composition of plasma & CSF?
pH (slightly more acidic in CSF) & osmolarity
What is different in the composition of plasma & CSF?
CSF - very LOW protein levels
At what level is the BBB present?
Level of CNS capillaries
Why is the BBB important?
CNS neurones sensitive to local envrionment - homeostasis is key for the brain
3 types of capillaries?
Continuous
Fenestrated
Sinusoid
From what are the CNS capillaris derived from?
Derived from surface pial vessels
What happens to the BBB capillaries the deeper it goes?
Extensive tight junctions at endothelial cell-cell contacts
remember capillary surrounded by endothelial and then pericytes
Importance of the change in property of BBB capillary the deeper it goes?
Reduces solute & fluid leakage across the capillary wall
BBB proper?
The deeper into the tissue, the less permeable BBB
Little transcellular vesicular transport
Interendothelial junctions (IEJs)
More tightly knit - endothelial cells overlap on each other to give a tighter fit
Other than pericytes what else are BBB capillaries covered with?
Astrocytes - ‘end-feet’
Which part of the CNS do blood-borne infections normally affect?
Meninges - as vessels are NOT BBB
Some evidence shows that loss of BBB can be good - why?
Can help with clearing some infections by allowing immune cells across
Example of lipophillic molecules that can cross the BBB?
O2
CO2
Alcohol
Examples of hydrophillic substances and specific transport mechanisms needed to cross BBB
Water - AQP1/4 channels
Glucose - GLUT1
AA - 3 diff transporters
Electrolytes - specific transporter systems
Area of the brain that lacks BBB? Where it is found?
Circumventricular organs (CVO)
Found close to the ventricles
What are the capillaries of the CVOs like?
Fenestrates (therefore leaky)
Why do the CVOs capillaries have fenestrated type?
Need to sample blood
OR
secrete into the blood itself
Relationship between CSF and CVOs?
Ventricular ependymal lining close to the CVOs often MUCH TIGHTER than other areas
To LIMIT exchange between them and the CSF
Area posterma?
Samples plasma for toxins - induces vomiting if found (example of CVO)
Antihistamines and BBB?
H1 blockers are hydrophobic so cross BBB by diffusion
As histamine invovled in wakefullness can cause people to become drowsy
What have been changed about the antihistamines in regards to the BBB?
2nd-generation antihistamines
Are POLAR (have a hydrophillic attachment) so do NOT readily cross the BBB so do NOT cause drowsiness
Issue with giving dopamine to treat Parkinson’s Disease?
Need to raise dopamine levels in brain to treat PDs
BUT
Dopamine CANNOT cross the BBB
Issue with L-DOPA?
L-DOPA CAN cross the BBB via. aa transporter
BUT
Most of it is converted to dopamine peripherally so LESS AVAILABLE to access the brain
How to overcome the issue with L-DOPA?
Co-administer with DOPA decarboxylase inhibitor
CANNOT cross BBB so does NOT interfere w conversion of L-DOPA in the brain
Example of DOPA decarboxylase inhibitor?
Carbidopa