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Neuro COPY > Neuro 5: Regulation of blood flow (BBB) > Flashcards

Neuro 5: Regulation of blood flow (BBB) Flashcards

1
Q

T/F: the brain has highest o2 consumption in body

A

False- kidney is higher. brain 3 ml 02/min per 100g , kidney 5ml o2/min per 100g

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2
Q

What is the blood flow to the brain not o2 but blood flow

A

55ml/100g tissue/minute

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3
Q

What % is the brain of: body weight, cardiac output, o2 consumption

A

Weight: 2%, CO: 15%, o2 consumption: 20%

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4
Q

Conseuquences of blood flow being reduced by more than 50%

A

Insufficient o2 delivery and impaired function

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5
Q

t/f 10 seconds of Cerebral Blood Flow (CBF) interruption will result in unconsciousness

A

t: in fact, it only takes 4 seconds of interrupted CBF f ro unconsciousness, and after a few minutes tissue damange

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6
Q

What is syncope and what are the causes

A

Fainting due to inadequate CBF

Low BP, postural changes, vaso-vagal attack, sudden pain, emotional shock. All result in temporary reduction of CBF.

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7
Q

What % of body’s glucose does brain use

A

60%

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8
Q

Why is glucose vital to brain

A

It can’t store or sythesise or utilise any other energy source except ketone bodies in starvation

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9
Q

Signs of hypoglycaemia

A

Disorietation, slurred speech and impaired motor function

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10
Q

What is dangerously low glucose level

A

Below 2mM can cause unconsciousness, coma and death. Normal fasting levels are 4mM-6mM

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11
Q

Overall, how is cerebral blood flow regulated

A

By:
Mechanisms affecting TOTAL cerebral flow

Mechanisms relating activity to the requirement in specific brain regions by altering LOCALISED blood flow

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12
Q

How is total cerebral flow regulated (one of the two factors affecting CBF)

What is the effect of not enough overall blood flow to the brain

What is the effect of too much overall blood flow to the brain

A

AUTOREGULATION between MABP 60 and 160mmHg.

Stretch sensitive cerebral vascular smooth muscle:

  • CONTRACTS at high BP (to reduce flow)
  • RELAXES at low BP (to increase flow)
  • Note… this is not to control BP…. this is to allow blood to the brain….. so it’s the opposite of what is useful to control BP*

Below the autoregulatory range –>compromised function
Above the autoregulatory range –> increased flow, swelling of brain tissue, increased intracranial pressure

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13
Q

How is local blood flow regulated- give the 2 mechanisms (one of the two factors affecting CBF)

A

Local brain activity determines o2 and glucose demands, local changes required –> LOCAL AUTOREGULATION.

  1. Neural control
  2. Chemical control
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14
Q

Pattern of vascularisation within CNS tissue

A

Arteries or arterioles (bit unclear) enter CNS tissue from branches of SURFACE pial vessels.
The branches penetratrate into brain parenchyma, branch to form capillaries, drain into venules and veins which drain into surface pial veins

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15
Q

Outline how neural factors impact cerebral blood flow (this is mostly local)

A
  1. Sympathetics constrict MAIN cerebral arteries when arterial BP high
  2. Parasympathetic facial nerve produce slight vasodilation
  3. Central cortical neurones release vasoconstrictor neurotransmitters like the catecholamines.
    * 4. Dopaminergic neurones producing vasoconstriction- localised effect related to increased braina activity
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16
Q

Outline local regulation of CBF by dopaminergic neurons

A

Innervate penetrating arterioles and PERICYTES , divert cerebral blood to high activity areas, causes contraction of pericytes via AMINERGIC and SERETONINERGIC receptors

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17
Q

What are the functions of pericytes

A

Cells that wrap around capillaries- have immune, transport and contractile function (TIC)

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18
Q

Outline chemical regulation of local CBF

A

CO2 (indirect), increased H+ or lactic acid or other acids, NO, K+, adenosie, anoxia all VASODILATE.

Kinins, prostaglandins, histamine and endothelins also have an effect

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19
Q

How does CO2 increase local CBF?

A

NOT DIRECTLY
It passes from the blood across the endothelium into the VSM, or from brain tissue around the vessel into the VSM.
Then converted by carbonic anhydrase, with water into H+ and HCO3-.
High H+ means decreased pH which relaxes the contractile smooth muscle cells and increases blood flow.

KEY: CO2 is dervied from neural metabolic activity

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20
Q

T/F: H+ ions within the blood vessel will stimulate relaxation as it indicates increased neural metabolic activity

A

FALSE! H+ within the blood vessel cannot pass through the endothelium into the smooth muscle to cause relaxation. However, H+ from neural tissue surrounding the vessel (formed from CO2 and H2O and carbonic anhydrase) can go to smooth muscle and cause relaxation

21
Q

How are local changes to CBF useful

A

Can look at the changes in imaging and map brain activity using PET and MRI

22
Q

State the fluid types in the brain

A

Blood, CSF and ECF

23
Q

Where is CSF produced

A

Choroid plexus lining ventricles.

24
Q

What is choroid plexus

A

Ependymal cells line all the aqueducts and ventricles, in some parts of the ventricles, the lining is modified to form branched VILLUS structures= choroid plexus

25
Q

T/f: Ependymal cells often ciliated

A

T

26
Q

How is CSF formed

A

Leaky capillaries, but not all of what leaks out of the capillary becomes the CSF- there are very tight junctions on the EPENDYMAL cells, so they don’t let everything pass from the blood into the ventricles

27
Q

State the path of CSF

A

secreted into lateral ventricles
then, via the interventricular foramina (i.e. a channel from each lateral ventrical to the 3rd ventricle), to the 3rd ventricle,
then via the cerebral aqueduct to the 4th ventricle, then into the subarachnoid space via medial and lateral apertures

28
Q

Volume of CSF

A

80-150ml

29
Q

Function of CSF

A

Protection, nutrition of neurons and transport of molecules

30
Q

Difference in composition in CSF vs plasma

A

In CSF: Less K+, more Mg+, LESS PROTEIN but same osmolarity

pH slightly lower more acidic

31
Q

CSF has little protein- why is it clinically imprtant

A

Increased proteins indicates infection (antibodies)

32
Q

How did we find about BBB

A

When we injected dye it accumulated in most tissues apart from brain and retina

33
Q

Why is BBB needed

A

Neuronal activity sensitive to the composition of local environment, so CNS needs to be protected from fluctuations in blood composition

34
Q

At what level is the BBB

A

Level of CNS capillaries

35
Q

Differentiate fenestrated and sinusoid capillaries

A

Fenestrated- holes but in tact BM

Sinusoids- large spaces betwen cells (intercellular gaps) and incomplete basement membrane

36
Q

What exactly is the BBB

A

BBB is the extensive tight junctions between endothelial cell-cell contacts in the penetrating branches of surface pial vessels, reducing solute and fluid leak across capillary wall

Think about those penetrating arterioles branching from pial vessels:

The surface pial vessels are permeable to most small molecules but have reduced passage of proteins across from blood to the neural tissue

In the branches which penetrate, there is drastically reduced passage of cellular elements and it’s impermeable to most hydrophilic molecules.

Further down the penetrating branches, there is negligible permeability, polarized phenotype and this is the site of active drug exclusion

37
Q

T/F: there is little transcellular and paracellular transport across BBB

A

T- little vesicular transport as well. Continuous type capillary

38
Q

Aside from the endothelial tight junctions, state other differences between peripheral and BBB capillaries

A

BBB covered with pericytes, peripheral capillaries have sparse pericytes

BBB capillaries covered with end-feet from astrocytes

39
Q

Which solutes are excluded by the BBB

A

In particular, hydrophilic ones.

e.g. glucose, AAs, many antibiotics, many toxins

40
Q

How does BBB control exchange of hydrohilic substances

A

SPECIFIC MEMBRANE TRANSPORTERS- influx and efflux transporters

41
Q

Why is meninges more commonly affected by blood borne infections. Counterintuitively, why could loss of BBB help with clearing infection

A

Meningeal vessels do not contain the BBB

Breakdown of BBB can allow immune cell access

42
Q

How does BBB deal with lipophilic molecules

A

it doesn’t, really….. o2, co2, alcohol and anaesthetics cross BBB. Access or removal via diffusion down conc. gradient

43
Q

How do the following substances enter the BBB

Water
Glucose
AA
Electrolytes

A

Water- aquaporin AQP1 and AQP4
Glucose- GLUT1
AA- 3 different transporters
Electrolytes by specific transporter systems

44
Q

What are the circumventricular organs

A

Areas close to ventricles which have fenetrated capillaries.

The ependymal cells lining the ventricles are even tighter here than in rest of brain to stop movement of fluid from the leaky capillaries into the CSF

45
Q

Why do CVOs exist

A

They are invoved in secreting into the circulation or need to sample plasma (e.g. pituitary gland and median eminence secrete hormones, or the area postrema samples plasma for toxins and induces vomiting), other areas involved in sensing electrolytes and water intake

46
Q

When can BBB breakdown occur

A

Strokes, inflammation, trauma, infection

47
Q

New vs old antihistamines and BBB

A

Old ones were hydrophobic, cross BBB and cause drowsiness (as histamine important in alertness and wakefulness) , these are now used for over counter sedatives
New ones are hydrophilic

48
Q

How does BBB affect treatment of Parkinson’s

A

Because you want to give dopamine, but dopamine doesn’t cross BBB

So you could give L-DOPA, which does cross the BBB, but if you do most will be converted to dopamine in the blood by DOPA decarboxylase

So you give them L-DOPA with a DOPA decarboxylase inhibitor called Carbidopa…. and the inhibitor is designed not to pass through the BBB so it stops conversion inthe blood (allowing L-DOPA to enter brain) but not in the brain! C

Neuro COPY (16 decks)

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