Blood supply to the central nervous system Flashcards
Why must blood flow to the brain be maintained and what happens when flow is inhibited over a few seconds to minutes?
The brain has high oxygen and glucose demands - it consumes 10-20% of the CO and 3ml/100g/min of oxygen.
If the brain doesn’t recieve oxygen for a few seconds - syncope
A few minutes - brain damage
BRAIN CANNOT USE LIPIDS, ONLY GLUCOSE AND KETONES DURING STARVATION
What is normal and abnormal (coma, unconsciousness and death) blood glucose levels?
normal - 4-6mM
abnormal - >2mM
What does cerebral blood flow autoregulation mean?
The total CBF is auto regulated in the MABP range of 60 - 160mmHg
Above and below this pressure, the CBF cannot be maintained
How does cerebral blood flow autoregulation occur?
Stretch-sensitive cerebral vascular SM contracts at higher BPs and relaxes at lower BPs
What is local cerebral blood flow autoregulation?
Local brain activity determines the local O2 and glucose demands, therefore local changes in blood supply are required
What are the two types of local cerebral blood flow regulation?
neural and chemical
What are the different components of the neural local control system of CBF regulation?
Sympathetic nerve innervation – vasoconstricts when MABP is high.
PNS facial nerve innervation – slight vasodilation
Central cortical neurones – release vasoconstrictor NTs such as catecholamines
Dopaminergic neurones – local vasoconstrictive effects
How do dopaminergic neurones cause vasoconstriction?
They innervate penetrating arterioles and pericytes (brain macrophages) around capillaries
They may participate in diversion of cerebral blood to areas of high activity
Act by causing contraction of pericytes via aminergic and serotoninergic receptors
Describe the vasculature of the CNS
Arteries from the pia mater penetrate into the brain tissue and branch to form capillaries.
These drain into venules/veins -> pial vessels
What are the different components of the chemical local control system of CBF regulation?
CO2 (Indirect - Vasodilator)
pH (Vasodilator)
NO (Vasodilator)
K+ (Vasodilator)
Adenosine (Vasodilator)
Anoxia (Vasodilator)
Other (i.e. kinins, prostaglandins, histamine - Vasodilator)
How is CBF affected by CO2 levels?
The increase in H+ decreases the pH inside the VSMCs which causes the cell to constrict resulting in vasoconstriction.
The H+ can be derived from the (higher) CO2 in the blood (NOT directly from H+ in the blood) or from increased neural metabolic activity (directly).
Describe where CSF is produced and the pathway it follows
- Produced by the choroid plexus (modified ependymal cells that ordinarily line the ventricles)
- The capillaries are leaky but adjacent ependymal cells have extensive tight junctions
- CSF is secreted into the lateral ventricles
- 3rd ventricle (via interventricular foramina)
- 4th ventricle (via cerebral aqueduct)
- subarachnoid space via medial and lateral apertures
What is total CSF volume?
80-150ml
What are the functions of CSF?
protection, nutritional, transport
What is the composition of CSF in comparison to plasma?
Similar pH (slightly higher in plasma) and osmolarity but importantly very low protein levels
K+, Ca2+, aa - CSF lower
Mg2+ - CSF higher
What are the three types of capillaries?
continuous, fenestrated and sinusoidal
Where do the capillaries of the CNS tissue originate from?
surface pial vessels
What is the blood brain barrier?
BBB capillaries have extensive tight junctions at the endothelia cell-cell contact zone – reduces leakage. Deeper into the tissue as the capillaries move deeper, the permeability decreases until the blood brain proper is present.
What are some structural features of the BBB?
Interendothelial Junctions (IEJs) – the IEJs are much more tightly knit and ‘torturous’ (the endothelial cells overlap on each other to give a tighter fit)
BBB capillaries are covered by “end-feet” from astrocytes which help maintain the BBB properties.
Which molecules can cross the BBB?
lipophilic ones - oxygen, carbon dioxide, alcohol
Describe how different molecules are transported across the BBB?
water - aquaporins
glucose - GLUT1
amino acids - 3 transporters
electrolytes - specific mechanisms
What are circumventricular organs?
In some places in the brain, it is necessary for capillaries to lack BBB properties – i.e. pituitary gland.
These capillaries are often fenestrated and are present as the CVOs often need to sample blood or secrete into the blood itself.
Found close to the ventricles
What is the clinical importance of the blood brain barrier?
Many therapeutic drugs cannot access the brain whereas many access the brain too readily and can cause adverse effects so it must be monitored.
How do old and new anti-histamines compare?
Old-fashioned H1-channel blockers are hydrophobic and so would cross the BBB and cause drowsiness (as histamine is a drug that keeps you alert).
Second-generation antihistamines are now polar and so do not cross the BBB so no drowsiness.
