4: Blood flow regulation and blood brain barrier Flashcards
What happens after a few secounds after loss of blood flow to the brain and after a few minutes?
- After ca. 4 secounds: unconciousness
- After a few minutes: irreversible brain damage
What is a Syncope?
Syncope= fainting
–> Result of a temporary reduction or disrubtion of blood flow to the brain?
What are normal blood glucose levels?
Which level of blood glucose is potentially fatal?
Normal levels: 4-6mM
if it falls below 2mM:
- can result in unconciousness, coma, death
Which two mechanisms regulate cerebral blood flow?
Autoregulation of blood flow
- via contraction/dialaiton of cerebral arteries, arterioles to maintain even blood flow
Local regulation of blood flow via
- neural control (e.g. SNS/PNS)
- chemical control (waste products)
Explain the autoregulation of total cerebral blood flow
Autoregulation between 60-160 mmHg MAP
- via stretch-senstitive cerebral vasculature:
- Contracts at high pressures, relaxes at low BP
Above or below the MAP range it can lead to too little blood flow to brain –> fainting or too much leading to a rise in intracranial pressure (dangerous)
Which two control mechanism determine local autoregulation of the brain?
Local mechanisms influenced by local brain activity and need for Oxygen and nutrients
There are
- Neural control mechanisms
- and Chemical control mechanisms
Which local neural control mechanisms are ther?
How important are they?
4 possible mechanisms
-
SNS stimmulation to main cerebral arterys
- vasoconstriction, normally only at hight blood pressure
-
PNS/Facial nerve stimmulaiton
- slight vasodilation
-
Central cortical neuronnes
- releasing vasoconstrictive neurotransmitters (e.g. adrenaline)
-
Dopaminergic neruones
- vasoconstriction (local effect, may contribute to diversion of blood flow to areas with high activity)
Overall: Neural control is not well defined and importance is uncertain!
Which chemical factors influence local blood flow to brain tissue?
Which effect do they have?
- CO2
- pH
- NO
- K+
- Adenosine
- Anoxia
- Other e.g. histmines, prostaglandines etc
–> All have a vasodilatora effect on blood flow! (Are waste products –> when high activity–> more waste products –> more blood flow)
Explain how CO2 influcences local blood flow to brain tissue
CO2 is produced as metabolism product:
- diffuses into Vascular Smooth Muscle
- Carbonic anhydrase: produces H+
- causes relaxation of SM
–> vasodilaiton –> increased blood flow
How do choroid plexi produce CSF?
They filtre the blood plasma and make it the composition the CSF has
What is the function of the Blood-brain barrier?
Neurones are highly sensitive to environmental factors
- CNS needs to be protected from fluctuation of the blood/body
Homeostasis is key!
What are pial vessels?
What do they give rise to?
Blood vessels on the surface of the brain, surrounded by CSF
They give rise to smaller arterys that eventually penetrate the brain tissue
How far is the maximal distance between a neuron and a blood vessel?
Maximal 100µm (one cell about 20)
–> Very dense capillary network!
Which structural componenets contribute to the blood brain barrier?
- Extensive tight junctions at endothelial cell-cell contacts
- Pericytes (cells associated with capillaries) densly cover capillaries in CNS
- Astrocyte processes cover capillaries
Which substances can cross the blood brain barrier?
Lipohilic molecules can cross membranes of cells and therefore blood brain barriers
- Hydrophilic molecules require special transport mechanisms
What are circumventricular organs?
Orangs, where it is neccessary for the BBB to be leaky, or highly permeable
–> e.g. Median eminence in the Pituitary
How is the increased leakyness of the (fenestrated) capillaries in circuventricular organs compensated?
The ventricular ependymal lining close to these areas can be much tighter than in other areas, limiting the exchange between them and the CSF
Why is sometimes an increased leakyness of capillaries required in the brain?
Need to communicate with outside world:
- the posterior pituitary and median eminence secrete hormones
- the area postrema samples the plasma for toxins and will induce vomiting
- others are involved in sensing electrolytes and regulate water intake.
Explain the importance of the BBB in pharmcokinetics at the example of parkinson treatment via dopamine increase
Question: Do you want the medication to cross the BBB?
In Parkinson YES!
–> Additional L-Dopa is given (can cross BBB), which is converted to Dopamine
But most of it is converted periopherally where you would not need the additional dopamine so:
coadministration with DOPA decarboxylase inbibitor that cannot cross the BBB
