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Block 3 Up To Quiz 1 > Blood Brain Barrier= Neuroscience and Pharmacology > Flashcards

Blood Brain Barrier= Neuroscience and Pharmacology Flashcards

1
Q

Major subdivisions of nervous system operate in

A

different chemical environments

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2
Q

bran and spinal cord chemical environment

A

-under protect of blood brain barrier which separates CNS from rest of body

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3
Q

Peripheral nervous system chemical environment

A
  • PNS outside blood brain barrier

- activity modulated in pt by fluctuations of chemical environment

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4
Q

Chemical environment ANS and ENS

A
  • changing chemical environment of ANS and ENS contribute to sensory input to CNS
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5
Q

Blood brain barrier limits access of what to CNS

A
  • nutrients, ions, drugs, other chemicals
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6
Q

Choroid plexsus epithelial cells provide

A
  • another barrier and secrete CSF acting as liquid fusion for brain
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7
Q

What gets delivered to brain and taken away from brain by circulatory system

A

Oxygen, glucose, essential amino acids delivered; CO2 removed

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8
Q

blood to brain

A

heart -> internal carotid
OR
heart -> vertebral -> basilar artery

-> circle of willis -> larger arteries branch to follow sulci and fissures -> dip into brain tissue

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9
Q

blood draining form brain

A

collects in sinuses (largest = dorsal sagittal sinus) drains via maxillary vein

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10
Q

Needs of brain

A
  1. Oxygen
  2. Special nutrient needs
  3. Glucose
  4. Water
  5. Gas exchange
  6. Circulation of blood
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11
Q

brain need for oxygen

A

brain ischemia of less than 1 min = unconscious; ischemia for a few min= fatal

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12
Q

brain special nutrient needs

A
  • 50kg mammal brain uses equivalent of total energy typical stored in liver as glycogen
  • brain glial cells limited capacity to store glycogen
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13
Q

brain under starvation conditions

A

will slowly adapt to use ketone bodies for energy

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14
Q

what does brain use energy for

A

maintain active transport of ions (including Na+ and K+ and also H+?) to maintain ionic gradients that allow:

  • neurons firing action potentials
  • facilitated diffusion for uptake essential amino acids
  • facilitated reuptake NT and precursors from synapse
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15
Q

Glucose exchange brain

A
  • uncharged D-glucose enters brain via facilitated diffusion

- CSF glucose level always less than systemic glucose concentration

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16
Q

brain metabolism

A

-brain has > 90% aerobic nutrient metabolism facilitated by constant perfusion oxygenated blood containing glucose

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17
Q

H20, O2, and CO2 exchange brain

A

freely diffuse between blood and brain following individual concentration gradient
- H20 uses aquaporin 4 to cross btwn

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18
Q

circulation of blood in brain

A
  • brain 1-2% body mass and gets 15% resting cardiac output
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19
Q

how does brain get rapid delivery of nutrients and drugs

A
  • high perfusion rate and high vascularization contribute to rapid delivery of nutrients and drugs to brain
  • perfusion rate maintained near constant 50ml/min/ 100gm tissue when systemic BP varies over lg range
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20
Q

mechanisms playing role in brain perfusion

A
  1. Brain metabolism
  2. Potassium ions and glutamate released from activated neurons
  3. Neural (ANS) control via symp nerves
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21
Q

brain metabolism role in brain perfision

A

brain metabolism -> lower pH -> drop PO2 -> vasodilation

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22
Q

potassium ions and glutamate released form activated neurons

A

stimulate astrocytes to release vasoactive substances -> capillary endothelial cells increasing in luminal diameter

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23
Q

Atrocyte role in capillary diameter

A
  1. Glutamatergic neurons release glutamate
  2. stimulate astrocytes to release vasodilatory factors
  3. vasodilatory factors secreted by astrocytic end-feet
24
Q

CNS (brain and spinal cord) contained in what

A

dura/ meningeal sac

25
Q

Layers of meningeies forming protective sheath around CNS

A
  1. Dura
  2. Arachnoid layer
  3. Pia cell layer
26
Q

Dura mater

A

Two cell layer around brain:
-fibrous periosteal dura (collagen and elastin) (adheres to cranial bones) is outer layer
- inner menial layer ensheath cr nerves as they pass from skull
- Septa= formed by sheets dura= separate major subdivisions of brain
Spinal Dura Matter:
- Only meningeal layer

27
Q

Arachnoid layer

A

Delicate membrane between dura and pia layer

28
Q

subdural space

A

between dura and arachnoid membranes (potential space?)

29
Q

Pial cell layer

A
  • ensheaths brain and spinal cord

- provides some structural support for blood vessels

30
Q

subarachnoid space

A
  • space between arachnoid membrane and pia
  • filled with CSF
  • contains larger blood vessels of brain and cistern
31
Q

what maintain chemical microenvionrment of brain

A
  • blood brain barrier

- near constant CNS microenvionrment

32
Q

blood brain barrier formed by

A
  • specialized brain capillary endothelial cells

- astrocyte end feet (encircle endothelial cells)

33
Q

what maintains near constant CNS microenvionrment

A

choroid plexsus epithelial cells lining brain ventricle

34
Q

endothelial cells blood brain barrier

A
  • no large fenestrations
  • tight junctions
  • both in brain capillairies = endothelial cells blood brain barrier?*
35
Q

Astrocytes blood brain barrier

A
  • glial cells provide second set cell membranes by ensheathing brain capillaries; these = additional cells that must be transferred and second intracellular compartment where cell metabolic process can transform rendering substances
  • Glial cells take up and redistribution excess interstitial K+
  • Glial cells respond to neurotransmitters released at synapses and communicate local environmental changes to neurons in area of neuropil they envelope
36
Q

blood brain barrier fx

A

protect brain from chemical environment of rest of body

37
Q

Blood brain barrier and transporteres

A

contains membrane bound transporters to maintain extra cell environment in CNS

  1. Transporters for essential amino acids and D-glucose
  2. ATP-dependent active transporters
  3. Aquaporins to bring water across membrane
38
Q

ATP-dependent active transporters what does it require and what does it provide

A

1/5th glucose goes to maintaining activity of ATP-depenedent active transporters:

  1. Active transport Na+, Ca2+, K+ maintains ion gradient across cell membrane which lets body
    - maintain neuronal cell excitability
  2. ATP-dependent H+ ion transporter
    - Drive amino acid transport and facilitate re-uptake of neurotransmitters
39
Q

Glutamate and GABA removal from synaptic cleft and concentration in synaptic vesicles

A
  • removal from synaptic cleft via facilitated diffusion

- concentration in synaptic vesicles via H+ ion gradient established by ATP-dependent H+ ion transported

40
Q

How do drugs and other substances cross blood brain barrier

A

common pharmicokinenetic principles and with aid of cellular proteins

41
Q

what delivers nutrients and drugs to brain

A

large perfusion area of cerebral vasculature

42
Q

what easily crosses BBB

A
  • lipophilic drugs

- non-ionized forms drugs

43
Q

Types cellular protein aids for crossing BBB

A

Carrier proteins/ ion gradient-dependent facilitated diffusion:
- ex. amino acids and D-glucose
Active transporters
- ex. K+ ions removed from CSF by Na+/K+ ATPase

44
Q

important factors determining ability of drug to get into CNS

A
  • oil/water partition coefficient (bc high lipophilic cross easily)
  • blood pH for some drugs (bc pH governs degree ionization and non-ionized forms drugs cross BBB)
45
Q

substances that don’t cross blood brain barrier in normal adult mammals

A
  • Albumin
  • Globulin
  • Transferrin
  • IgG
  • IgA
  • IgM
46
Q

Where/ When is blood brain barrier more leaky

A
  1. Young age (neonates and young animals don’t have fully formed BBB)
  2. Region of circumventricular organs
  3. Pathologic BBB leakiness
  4. Clinician-induced hyperosmotic shock
47
Q

Region of circumventricular organs

A
  1. Hypothalmic region of median eminence and pituitary

2. Area postrema

48
Q

Area postrema

A

aka Chemotactic trigger zone or chemoreceptor trigger zone (CTZ or CRTZ)
- this is area where neurons express chemosensory that sample environment of IVth ventricle and transmit info to V+ reflex center in brainstem

49
Q

pathologic blood brain barrier leakiness occurs with

A
  1. infectious dx of meninges
  2. high fever
  3. hepatic dxs- high plasma bilirubin
50
Q

hyperosmotic shock

A
  • clinician induces this to get chemotherapeutic agents to brain by injecting hyper osmotic solution with drug
51
Q

Cerebrospinal fluid-blood barrier

A
  • choroid plexsus epithelial cells form this and serve barrier and transport fx; these cells= impermeable to plasma proteins and amino acids
  • Tight epithelium
52
Q

Choroid epithelial cells and CSF

A

regulate fluid volume and ion concentration and allow gas exchange and manufacture CSF

53
Q

Fxs CSF

A
  • shock-absorber
  • provide constant chemical microenvionrment (brain extracellular fluid protects CNS synapses from variable ionic environments of blood)
54
Q

Choroid plexus tissue

A
  • located in ventricles of brain
  • CSF continuously secreted, circulates throughout ventricles and flows along spinal column and throughout spinal canal
  • CSF exits ventricles via openings leading to sinuses
55
Q

CNS pharmacology considerations

A
  1. Drugs excluded from BBB bc pharmacokinetics can be used for peripheral nervous system
  2. Little compartmentalization in brain so drug crossing BBB interacts can interact with all potential receptors
  3. Neural circuitry complex includes excitatory and inhibitory neurotransmitter signaling in feed-forward and feedback configurations so behavioral responses to CNS drugs hard to predict

Block 3 Up To Quiz 1 (24 decks)

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