Delivery and utilisation of energy in the brain Flashcards
Brain at rest consumuption:
- 60% of glucose utilisation of human at rest
- 20% of oxygen utilisation
- 120 g of glucose a day
- 1760 kJ / day = 20 Watts = dim light bulb
Astrocytes
Type of Glial cell
wrap around the blood vessels
NT Release 1
- Action potential arrives
- Presynaptic cell depolarises
- ‘physiological’ depolarisation
- Release by vesicle fusion
- Vesicles each contain
- 250-5000 molecules of Glutamate
NT release 2
- Diffusion across the synapse
- Activation of next cell
- Na+ enters cell
- K+ released
- Post synaptic cell depolarises
What 2 key tasks remain after NT release?`
- REPOLARISATION of cells
- REMOVAL OF NT
Features of Repolarisation
- Requires ATP for energy
- Net REMOVAL of cations from cell - ELECTROGENIC
GLUTAMATE
- Highly active at receptors
- Depolarises post-synaptic cells
- they can not pass on new messages
- Can swell and die
- Gives rise to major energy use (75% in primates)
EFFECTIVE REMOVAL OF GLUTAMATE IS VITAL
What takes up Glutamate?
what is the uptake powered by?
Astrocytes
uptake powered by ionic gradients running down
hence Na/K ATPase - needs ATP
What happens to the Glutamate inside the Astrocyte?
-
Glutamate is converted in to Glutamine
- Requires another ATP
- Glutamine exported and taken-up pre-synaptically
- Converted and packed into vesicles - requires ATP
What is Neurovascular coupling?
What does activity in the neuron lead to?
Neurovascular coupling
- name of process in which local neuron activity is monitored and then subsequent changes in cerebral blood flow occur
Activity leads to:
- increased blood flow to deliver OXYGEN and GLUCOSE
astrocytes uptaking the NT are made aware of the energy requirements and are responsible for sending numerous messages to the blood vessels to change blood supply
GLUCOSE
- only source of energy for the brain
- transported into the glial cells mainly
- conversion into glc-6-phosphate needs energy
- from here either
- metabolised
- or stored as glycogen
- from here either
- N.B glycogen stores limited, rapid turnover, imp local energy source “brain’s battery”
Brain when can it work/can’t work?
Brain is able to work in the ABSENCE OF OXYGEN:
- e.g. in hypoxia or stroke etc
- lactate/NAD+ production, allows glycolysis to continue
Brain CAN’T work in the ABSENCE OF GLUCOSE
Where does glucose metabolism take place?
Cytosol
What are the 2 fail safe anatomical features of the Brain’s circulation?
- Circle of Willis
- surface network : Leptomeningeal collateral circulation
Leptomeningeal Collateral Circulation
- like a fishing net draped over the brain
- supplied by 3 major inputs:
- MCA, ACA, PCA
- From the meshwork that sits over the hemispheres
- penetrating arteries descend into cerebral cortex and white matter
- perforating arteries from proximal vessels supply the deep grey matter
What depends on normal B.P?
The Leptomeningeal collateral circulation
does its best if the Middle Cerebral Artery is occluded
If B.P. is lowered then the leptomenigeal collateral circulation can’t do as good a job and the middle territory will suffer
What is the Penumbra?
The area around the core
here the blood flow is low but not too low like in the core
How long does it take before the Penumbra deteriorates and then what happens?
- 12-48 hours
- then it is recruited into the expanding core
- more brain tissue dies
Core Ischaemia
- Perfusion BELOW the survival threshold
- ~10ml/100g/min
- below this
- all cells will die (neurones and astrocytes)
- serious capillary damage
Penumbra
- The “ grey ” area around the core, nearer the collaterals
- Perfusion partly reduced, below the FUNCTION threshold only (function impaired but cells don’t die)
- Neuronal and synaptic function suppressed
- Responds to EARLY reperfusion - tissue will recover and not go into infarction
- Depends on glucose + glycolysis, which increases to generate the required ATP
WHy does the core expand
(without a drop in bp to reduce the collaterals)?
Due to SPREADING DEPOLARIZATIONS
these are PATHOLOGICAL
SPREADING DEPOLARIZATION
- K+ out
- Na+ in
- INput:
- flooding of the extracellular space with K+ and glutamate by neurons and astrocytes upstream in the wave - ripple effect
- Output:
- massive release of K+, allowing wave to propagate
- PATHOLOGICAL: suspends function
- Lasts 1-2 mins; needs ~10mins to recover
- All neighbouring cells depolarise, massive ATP use
- REQUIRES MASSIVE INFLOW OF BLOOD TO FIX THIS (huge energy requirement)
What is the normal brain respone to functional activity or a spreading depolarisation?
Hyperaemia
Increase in blood flow
what happens to bld glc levels after 1 depol?
how long will it take to recover
bld glc levels will fall
needs to repolarise
wont recover levels for 30 mins
What happens in the Penumbra when a depol occurs?
VASOCONSTRICTION in the microcirculation causing the blood flow to drop
Opposite to normal where it causes an increase in blood flow
Therefore it is vital to reperfuse quickly to try and restore function
How do neurones die?
- Due to lack of oxygen, no ATP production from Krebs cycle
- hence the Na/H antiporter stops working same with Ca antiporter
- in depol:
- Ca2+ and Na+ enter cell, H+ levels also increase as lactic acid builds up, small amount of K+ leaves
- Net osmotic effect, water goes in to cell with cations
- results in CYTOXIC OEDEMA; cell swells as water moves in
Main mechanism of spread of depol?
K+ leaking out and depolarising the surroundin cells
Why do brain’s swell with reperfusion?
Reactive hyperaemia
- Whole territory , dilates, so..
- More capillaries open, so Increase in brain volume..7
- Capillaries weak, and leak…
- Haemorrhagic conversion
Summary 1
The brain uses large amounts of energy, principally to:
- Repolarise neuronal membranes
- Maintain a cation imbalance (3Na+ outward / 2K+ inward) that keeps some water out of cells that keeps some water out of cells
- Re-uptake neurotransmitters from the synaptic space
Summary
Without Oxygen
- glucose breakdown to lactate yields only a fraction of the potential ATP yield
- That means much more glucose utilisation - 18x more
- Since the brain’s glucose store is very small (glycogen), it is heavily dependent on adequate glucose delivery from perfusion
Ischaemia
Defintion:
- Is a state in which perfusion no longer meets the metabolic needs of the tisssue
There are two collateral circulation systems that reduce the risk of ischaemia:
- Circle of Willis
- leptomeningeal collaterals
How was it that some of the weakness got better?
In the penumbra function
may recover function may recover with reperfusion with reperfusion (without this, the core will gradually expand into the penumbra by starting “tsunamis” around itself, so that the pneumbra area also infarcts)
Why did the brain swell soon after reperfusion?
Tissue in the ischaemic Core
- Will die unless reperfused “in time”
- May swell and bleed if reperfused too late
