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Neuroscience, Behavior and Social Sciences > Blood CNS Barriers in Homeostasis > Flashcards

Blood CNS Barriers in Homeostasis Flashcards

1
Q

Definition of pericyte

A

Cells that surround the brain capillaries and trap large macromolecules that have escaped from the lumen

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2
Q

Definition of simple diffusion

A

Diffusion via paracellular clefts

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3
Q

Definition of passive diffusion

A

Diffusion through the cell

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4
Q

Definition of the partition coefficient

A

Increased Pc => increased lipophilicity and uptake into BBB

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5
Q

Where is the blood brain barrier

A

At the level of the brain capillaries

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6
Q

Describe the vascular supply of the brain

A

2 carotid arteries
2 vertebral arteries

Circle of Willis at base of brain => pial arteries above pia mater

Penetrating arteries, branch off and penetrate brain tissue but not into pia mater
Penetrating arterioles
Intracerebral arterioles
Capillaries

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7
Q

Describe the brain capillary density in the brain

Why is this adaptation necassery

A

2500-3000mm3

  • no brain cell is 1-2 cell widths away from a capillary
  • v efficient for diffusion
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8
Q

Describe the structure of capillaries in the neurovascular unit

A

Monolayer of endothelial cells that form the paracellular cleft
Surrounded by pericytes and basal lamina

Basal lamina surrounded by end feet of astrocytes, neurones

Oligodendrocytes surround neurones

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9
Q

Describe the structure of the astrocytes within the brain

A

End feet of astrocytes form a perivascular sheet around the endothelium

Layer found under the pia mater and forms the glia limitans

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10
Q

What are the 5 functions of astrocytes

A
  1. energy and nutrient support of neurons
  2. ion and water homeostasis
  3. termination of synaptic activity
  4. maintenance of blood brain barrier
  5. sense [O2], [CO2] in tissue fluid and regulate breathing
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11
Q

What 2 structures found in brain capillaries to limit paracellular movement
Why are they present

A

Adherens junctions

  • adhesion molecules
  • cadherin, both attach to catenin => actin cytoskeleton

Tight junction

  • claudin, occludin
  • adhesion molecules both attach to zones occludentes => actin cytoskeleton

Limits substance movement between cells => stops simple diffusion

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12
Q

Describe passive diffusion through the blood brain barrier

How does partition coefficient relate to diffusion

A

Small lipid molecules and blood gases passively diffuse due to lipid bilayer

Increased partition coefficient => increased lipophilicity and uptake into BBB

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13
Q

Describe the diffusion of the drugs

  • morphine
  • codeine
  • heroin into the BBB and their actions
A

Morphine => not lipophilic, can’t enter
Codeine => lipophilic, can enter
Heroin => very lipophilic, can enter

Heroin in metabolised to morphine which can’t escape BBB with a long half life

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14
Q

Describe the 2 main types of transporter in the lipid bilayer
What are the functions of each main type

A

Solute carrier transporters (SLC)

  • faciliated diffusion
  • 2ndary AT

GLUT1 for D glucose
carriers for neutral AA, acidic AA, basic AA

ATP binding cassette (ABC)

  • efflux transporter out of brain
  • 1ary AT

P-glycoprotein

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15
Q

Describe the polarity of the AA transporters

A

Not all expressed on both sides of the membrane

Some cotransported with Na

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16
Q

Describe the structure of P-glycoprotein

Describe the drug properties that will be impacted by P-glycoprotein

A

Transmembrane domain
Binding sites in lipophilic region of bilayer

Drugs must be lipophilic to enter cell but will be extruded back into the blood

17
Q

Describe the process of non selective fluid phase endocytosis

A

Any molecule nearby the luminal membrane => vesicle => cytoplasm
Contents released on basal side

18
Q

Describe the process of selective receptor mediated transcytosis
What molecules are transported this way

A

Specific molecules bind to receptors
Triggers vesicle formation and carried to the other side
Receptor releases molecule on the other side

Insulin
Transferrin

19
Q

Describe the process of selective adsorptive transcytosis

What molecule is transported this way

A

+ve charged molecule attracted to -ve glycocalyx
Triggers vesicle formation and carried to the other side
+ve charged molecule released on the other side

Albumin

20
Q

Describe the metabolic barrier on the BBB via enzyme systems

What are the 2 main enzymes found here
How are substrates here generally processed

A

High [monoamine oxidase], [DOPA decarboxylase] embedded within membrane

Substrates hydrolysed and enter cell

  • either extruded out via efflux transporters
  • metabolized so it can’t pass through basal membrane
21
Q

What are the 4 functions of the BBB

Why is this important

A

Control molecule influx => brain ISF
Supplies brain with essential nutrients
Mediates efflux of waste
Restricts ionic/fluid movement

Protects brain from ionic fluctuations present in plasma
Stabilises ISF so conditions are optimal for neuronal function

22
Q

What are the main 3 structures involved in the blood CSF barrier

A

Choroid plexus in all 4 ventricles

Barrier formed by arachnoid membrane

23
Q

What is the function of the choroid plexus

A

Produce CSF

Synthesizes polypeptides => help regulate brain ISF

24
Q

Describe the structure of the choroid plexus

A

No tight junction in paracellular cleft between endotheium => leaky

Extracellular fluid space between endothelium and epithelium

Monolayer of choroid plexus epithelial cells form blood CSF barrier due to tight junctions

Tight junctions on CSF side but not as tight as in BBB

25
Q

Describe how CSF is excreted

A

NaKATPase on CSF side of epithelium
2ndary AT of NaH and HCO Cl
K, Cl, HCO3 leave via channels and transporters
Na movement followed by H2O via AQ1

26
Q

Describe the pathway of CSF flow in the brain

A

Released by choroid plexus => ventricles => sub arachnoid space
Moves by hydrostatic pressure differences (bulk flow)

27
Q

How does CSF leave the CNS

Why can’t CSF leave via the arachnoid mater

A

Subarachnoid space => arachnoid villus (1 way valve) => sup sagittal sinus

Can’t leave via the arachnoid mater due to tight junctions between overlaping cells

28
Q

What volume of fluid is found in the CSF and the ISF

What is the rate of fluid production in both the CSF and ISF

A

Total CSF = 140
Rate of fluid production = 350ul/min

Total ISF = 280
Rate of fluid production = 7ul/min

29
Q

What are the circumventricular organs

What are the 2 types and what do they do

A

Capillaries here have no tight junctions => v leaky
Found in the ventricles

Sensory
-senses changes in the blood

Neurohaemal secretory
-secretes substances into the blood

30
Q

Describe how Alzheimers can occur

A

Amyloid B removal process from the brain is damaged

-receptor mediated endocytosis can’t occur

Neuroscience, Behavior and Social Sciences (50 decks)

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