Regulation of blood flow to brain

Question 1

At what levels does oxygen levels have to fall to significantly impair brain function

Answer 1

under 50% you get impairment
Over 4s you faint
a few minutes is brain damage

Question 2

What is syncope?

Answer 2

faiting-common mannifestation of reduced blood supply to brain
eg: when you have low blood pressure, movement
Vaso-vagal attack, trauma

Question 3

How does hypoglycemia impact brain function?

Answer 3

fasting levels are 4-6mM
Most obvious in insulin-dependent T2DM
Disoriented, slurred speech, impaired motor function
->can happen to others of course

Under 2mM-faint, coma and death

Question 4

What 2 types of mechanism regulate cerbral blood flow ?

Answer 4

Mechanisms affecting body blood flow and local blood streams (local split in chemical and neural control
MABP of blood flow is autoregulated (between 60-160mmHg)

Question 5

What is the limit of cerebral blood flow autoregulation?

Answer 5

Between 60-100mmHg its all good
under 60 faint
Above 160-swelling of brain tissue, oedma-in a closed cranium-danger

Question 6

How does cerebral blood flow autoregulate?

Answer 6

Stretch sensitive sensors cause the vessel to contract when BP is high-limiting blood flow (keeping it normal)
And at low levels, automatically widen-regulate

Question 7

Describe the pattern of vascularisation of CNS

Answer 7

Larger vessels on the surface-in the Pia
Penetrating arterioles pass through the brain (dense capillaries network from there)
Drain from venules, and largers vessels on the surfeace

Question 8

Describe the neural factors impacting local cerebral blood flow

Answer 8

Sympathetic nerve stimulation to main cerebral arteries
PSNS stimulation (facial) for slight
Central cortical neruons-variety of vaso contrictors
Pericytes

Question 9

Describes the chemical factors impacting local cererbral blood flow

Answer 9

Obvious vasodilators (NO, kinins, prostaglandins, adenosine, etc)
But big role of CO2 and pH
Normal pCO2 around 40-but sigmoid curve with blood flow (small increase of pCO2 causes large increase in blood flow)
Caused by vasodilation

Question 10

How does CO2/pH affect local brain blood flow

Answer 10

Acts on vessels-vasodilate
H+ can pass Bloodbrainbarrier
But CO2 can pass to smooth muscle to make H+
And H+ made from metabolic activity of neurons also go to smooth muscle
All this means SMC has increase H+-causes them to dilate and increase blood flow
SO as soon as use an area, increase metabolic demands cause increase of CO2 and therefore blood flow

Question 11

Describe the movement and origin of CSF?

Answer 11

choroid plexusus are spike like vessel formations formed of leaky cappilaries in the ventricules. Cavity wall is tight but transporters take from blood whatever is needed
Produced in ventricules I/II, and then passes to III, then aqueduct to IV, then to allows entering the Pia, into brain via lateral apertures. about 140ml (and also go to spine via central canal)
Exit near the succulus, where arachnoid granulations”bugle out”

Question 12

What is the role of the CSF?

Answer 12

80ml-15-ml
Unsure if it provides nutrients because there is already blood, and CSF has less everything
But definitly used as a cushion/sitting area for the brain

Question 13

What does high proteins in the CSF indicate?

Answer 13

Meningitis (infection)

Or damage of the system causing a leak

Question 14

Why do we need a Blood Brain Barrier? Where does it happen

Answer 14

CNS need a stable environement-and need a barrier for it not to follow the fluctation of the body
Happens at the level of cappilarries-brain has very dense networks

Question 15

What particular characteristics of the endothelial cells allow for the BBB?

Answer 15

very tight junctions-numerous TJ between cells that allow minimal fluid escape from the cappilaries (get tighter as it exits the pia vessels)
Also junctions are tortuous (not straight)-restrictive
In addition, astrocytes contact the vessels, producing Grwoth factors to maintain the BBB
Everything has to pass by the cells-meaning anything not desired is refused (drugs, infections, toxins)

Question 16

What can pass throught the BBB?

Answer 16

Lipophilic molecules can just pass the cell barrier (O2, Co2, alcohol, aneathetics)-go just down their concentrations
Hydrophilics will have to pass by the cell (ions, molecules) have to pass via transporter (water by AQPR1/4), glucose (GLUT1), AA (via 3 transporter), electrolytes via various channels

Question 17

What are the CVOs in the brain?

Answer 17

Circumventricular organs
Some area, near ventricules, are immune from the BBB. Localised epithelium that are leaky, but ependymal are tighter so sorta compensate -they sample the plasma or produce hormones/signals to go into it
eg: Posterior pit

Question 18

What are the main clinical implications of the BBB breakdown?

Answer 18

CAn breakdown with stokes, inflammation, trauma -etc

can cause a lot of damage as suddently blood can freely enter

Question 19

Why is the BBB important in pharmacology?

Answer 19

NEed to decide if therapeutic drug needs to acess the brain or not
Sometimes shouldnt
Old H1 antihistamines (hydrophobic) could pass the BBB and would make you drowsy -now sold as nytol (new ones are polar)

But BBB can also be a problem-cant get dopamine to brain by BBB.-therapy for parkinsons
(work around is giving L-DOPA, wich looks like AA, but converted there) -but a lot gets converted outside of the BBB-so inhbiti those by carbidopa as the same time, and cardidopa cant pass the BBB