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A&P module 4 CNS > 4.5 BBB > Flashcards

4.5 BBB Flashcards

1
Q
  • There are no ____ between the brain endothelial cells: (general capillaries have “pores” in the endothelium) and neighboring endothelial cells are joined by ___ that “seal” the intercellular space
A

fenestrations, tight junctions

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2
Q

Endothelial cells in brain capillaries don’t take in materials from the blood via ____;

A

pinocytosis,

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3
Q

Brain capillaries have greater than the expected number of _____ for active transport (requires ATP) of specific molecules and Mitochondrial enzymes (MAO for example) can render unwanted substances inactive or impermeable

A

mitochondria

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4
Q
  • Brain capillaries are surrounded by a layer of astrocytic foot- processes. Astrocytes secrete ____ and this induces the expression of claudins in the tight junctions of the blood-brain barrier.
A

Angiopoietin -

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5
Q

The “tightness” of the tight junctions is directly proportional to the number of ____ that comprise them

A

claudins (and occludins),

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6
Q

Astrocytes server as a liaison between neurons and cerebral blood vessels- they release K+ during periods of high activity in the brain; typically in response to the excitatory neurotransmitter, ____ K+ activates KIR (inward-rectifier K+) channels in the cerebral arterioles, which cause them to dilate

A

glutamate -

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7
Q

Some small, localized areas of the brain lack a blood-brain barrier and all are located near a __
_and are described collectively as circumventricular organs

Capillaries in these areas are fenestrated and endothelial cells show evidence of ____ transport of materials

A

cerebral ventricle

pinocytotic -

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8
Q

Posterior pituitary gland
Median eminence of the hypothalamus
Chemoreceptor trigger zone
lack what?

A

Examples of areas lacking a BBB:

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9
Q

These areas either release neurosecretory products into the blood or are chemoreceptor areas that require access to substances in the blood

3

A

Posterior pituitary gland
Median eminence of the hypothalamus
Chemoreceptor trigger zone

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10
Q
  • Physiological significance of the blood-brain barrier: ($4 things)
A
  1. To maintain a constant chemical environment: neurons must be protected from fluctuations in levels of extracellular ions, neuroactive substances and growth factors
  2. To protect the brain from endogenous and exogenous toxins
  3. To prevent the escape of neurotransmitters into the general circulation and vice-versa
  4. Drugs that don’t cross the blood-brain barrier don’t produce CNS effects; this may be an advantage or a disadvantage
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11
Q
  • Factors determining movement across the blood-brain barrier
A
  1. Presence of specific transport mechanisms: glucose, amino acids, etc.
  2. Lipid solubility
  3. Molecular size
  4. The “metabolic blood-brain barrier”
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12
Q

, Parkinson’s disease, DOPA decarboxylase inhibitor - Some substances are transported from the plasma into brain capillary endothelial cells but are then ____, thus inhibiting uptake into the brain

A

, Parkinson’s disease, DOPA decarboxylase inhibitor - Some substances are transported from the plasma into brain capillary endothelial cells but are then ____, thus inhibiting uptake into the brain

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13
Q

L-DOPA is used to treat ____ as it is a precursor to dopamine, L-DOPA is transported into endothelial cells, but there it is converted into dopamine (DA) by DOPA decarboxylase; Monoamine oxidase (MAO) and aldehyde dehydrogenase rapidly convert DA into 3,4-dihydroxyphenylacetic acid (DOPAC), an inactive metabolite, effectively preventing L-DOPA from entering the brain so a ____ must be administered with DOPA to facilitate its uptake into the brain

A

Parkinson’s disease

DOPA decarboxylase inhibitor

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14
Q
  • Metabolic substrates that cross the blood-brain barrier

4

A
  1. Glucose
  2. Amino acids
  3. Essential fatty acids
  4. Cholesterol, nonessential fatty acids and blood
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15
Q

Glucose is transported from the plasma into endothelial cells and then into the interstitium of the brain by the ____ which is a a facilitative transporter (not ATP-dependent), therefore it can’t transport glucose against _____For glucose to move into the brain the blood glucose concentration must be ___ than the brain glucose concentration

A

GLUT1 glucose transporter, a concentration gradient, higher -

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16
Q
  • Amino acids are also transported across the blood-brain barrier by facilitated diffusion (specific transport proteins) via the ___ which transports large, neutral amino acids such as leucine or valine; also L-DOPA
A

L” system,

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17
Q

Similar to glucose transport, amino acid transport is dependent on a relatively ___ amino acid concentration in the plasma. Amino acids are used for protein synthesis, as neurotransmitters (e.g. glutamate, aspartate) and as neurotransmitter precursors in the brain (e.g. tyrosine, tryptophan)

A

higher

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18
Q
  • Essential fatty acids are those that cannot be ___ in the body (i.e., linoleic and linolenic acid) These fatty acids enter the brain via specific ____
A

produced, essential fatty acid transporters

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19
Q
  • Cholesterol, nonessential fatty acids and blood-borne lipoproteins do not enter the brain and therefore must be ____
A

synthesized by the brain

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20
Q

Most molecules are able to move freely between the interstitial fluid of the CNS and the CSF; there is no ___ between the interstitial fluid in the CNS and the CSF

A

diffusion barrier -

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21
Q

Because CSF is produced from plasma, to complete the protection of the brain there must be a ___ in addition to a blood-brain barrier

A

blood-CSF barrier

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22
Q

_____ produces about 80% of the CSF

A

Choroid plexus

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23
Q

The balance of the CSF (roughly 20%) is contributed by _______ that flows across the ependymal cell layer that lines the ventricles or across the pia mater on the surface of the CNS

A

CNS interstitial fluid

24
Q

Choroid plexus is a tissue present in ____. The structure of the choroid plexus (blood-CSF barrier) involves clusters of convoluted, fenestrated capillaries, a simple cuboidal epithelium surrounds the capillaries: these epithelial cells are joined by ____ and contain many mitochondria, and a basement membrane binds the capillaries to the cuboidal epithelium

A

all four ventricles, tight junctions

25
Q
  • Various body fluids are produced from plasma: glomerular filtrate in the kidneys, aqueous humor in the eye, sweat, saliva, and CSF among others
A

ultrafiltration

26
Q

Most of these fluids are produced by ____ which means some of the plasma is forced through a semipermeable membrane by hydrostatic pressure. These fluids have the same ionic composition as plasma, but are virtually free of protein and blood cells and the rate of formation of these fluids is related to BP.

A

ultrafiltration

27
Q

The implication of this is that the ionic composition of the CSF is ___ controlled than that of other body fluids. Also, CSF production doesn’t fluctuate because of changes in ___

A

more carefully, blood pressure

28
Q

Due to their tight junctions, ions are pumped, via transporters in the cuboidal epithelial cells of the choroid plexus, from the blood to the CSF The ___ is the primary transporter. Cl- follows the electrostatic charge of Na+; movement of these two ions, in turn, creates an osmotic gradient across the cell’s membrane. H2O follows these charged ions through aquaporins and HCO3- also gets pumped into the CSF but the concentration of HCO3- in the CSF is less than its concentration in the blood, therefore the CSF’s pH is ___ than that of the blood

A

Na+-K+ ATPase, slightly lower

29
Q
  • Blood flow to the choroid plexus is ____ higher than the blood flow to the brain tissue itself and ___ higher than the kidney
A

10x, 5x -

30
Q

The ____ of CSF compared with the brain reduces the effective mass of a 1500 gram brain to only about 50g

A

low specific gravity

31
Q

The interstitial fluid compartment of the brain is ____ with the CSF

A

continuous

32
Q
  • Movement of the ISF to the CSF can occur:
A

i. across ependymal cells → into ventricles
ii. across pia mater → into subarachnoid space
iii. via perivascular space, which are extensions of the subarachnoid space along blood vessels

33
Q
  • visible herniations of the arachnoid mater that protrude into the superior sagittal sinus
A

arachnoid granulations

34
Q

Excess ISF and/or CSF can then be reabsorbed via ___ in the superior sagittal sinus, where they enter the venous system. There are a few recently discovered ___ in the CNS (dura mater) that remove excess ECF

A

arachnoid granulations, lymphatic vessels

35
Q
  • Factors that contribute to CSF movement:
A

a. Hydrostatic pressure of CSF formation
b. Cilia on ependymal cells
c. Respiratory movements and pulsations of cerebral arteries

36
Q
  • CSF flow functions to:

5

A
  1. Maintain a stable environment within the brain
  2. To keep a steady-state with brain interstitial fluid
  3. Displace older fluid
  4. Remove waste products from the brain
  5. Act as a hydraulic shock absorber
37
Q

Most of the non-choroid plexus CSF production is the result of ____ by the brain (i.e., “metabolic water”) Metabolic H2O then crosses ependymal cells or the pia mater to become CSF. The rest is from

A

glucose oxidation, filtration of plasma -

38
Q

While the brain represents only about 2% of the total body weight, it receives ___ of the resting cardiac output and consumes about ___ of the O2 required by the body at rest, uses ___ of the glucose consumed by the body

A

15%, 20%, 25%

39
Q

The brain uses energy to:

A

Maintain ionic gradients
Synthetic tasks
Axonal transport of materials to and from the axon terminals
Cell volume regulation by the Na+-K+ pump
Glial cell activity

40
Q
  • Because so few substances are transported across the blood-brain barrier, the brain is highly dependent on ____, both for energy and as a precursor to other macromolecules
A

glucose

41
Q

At very low temps, blood viscosity ___ and blood flow ____ With cardiopulmonary bypass to maintain blood flow, neurons can tolerate relatively long periods of ischemia and hypoxia

A

increases, decreases

42
Q

A ____ decrease provides some degree of cerebral protection against ischemia and hypoxia
But at ___ below normal, the cardiovascular system begins to fail, compromising blood flow to the brain

A

2 to 3°C, 7 to 8°C

43
Q

If there is a ___ in O2 delivery, the brain can extract more oxygen from the blood (greater dissociation of O2 from hemoglobin)

A

decrease

44
Q

The brain is the least tolerant of ___ of all of the tissues in the body.

A

ischemia,

45
Q
  • Imbalance between the availability of ATP and ATP demand leads to:
A

a. Na+-K+ pump failure
b. Gradual depolarization with loss of excitability (i.e., accommodation)
c. Loss of cell volume control with swelling and eventual lysis

46
Q

Ketone bodies can be reconverted to ___ in the mitochondria

A

acetyl CoA

47
Q

During hypoglycemia (due to starvation, prolonged fasting or insulin overdose, for example), the brain can use energy released by the oxidation of ketone bodies: _____ and ____. Ketone bodies are water-soluble but when their concentration in the blood increases, their transport across the blood-brain barrier also increases

A

Acetoacetate and β-hydroxybutyrate

48
Q
  • ___ is also a precursor to nucleic acids, cholesterol, fatty acids, prostaglandins, acetylcholine, glycine, aspartate, glutamate and gamma-aminobutyric acid (GABA) in the brain
A

glucose

49
Q
  • Amino acids can enter the CNS but very little ____ occurs there
A

gluconeogenesis

50
Q
  • About 70% of the ATP produced in the CNS is consumed while maintaining ____ with the Na+-K+ pump (ATPase), Ca2+ pump, etc.
A

ion distributions/membrane potentials

51
Q

Under normal conditions, the requirements of the CNS for energy are met by glycogenolysis in the liver, but the majority of the time the brain uses glucose as its only fuel. Glucose uptake by neurons is not ___; only a blood glucose level of at least 50 mg/dl is needed to maintain uptake

A

dependent on insulin

52
Q

Fatty acids can be a major fuel source in many tissues, but only ____ cross the blood-brain barrier which are used almost exclusively as precursors in the synthesis of “structural lipids” (membrane phospholipids, myelin, etc.)

A

essential fatty acids

53
Q
  • The brain is less tolerant of hyperthermia than it is of hypothermia. Cerebral metabolic rates increase as temperature rises to ___ and at about ___, many enzymes become inactivated by heat, metabolism decreases, and neuronal damage occurs
A

40 - 42°C, 43°C

54
Q

Synthetic tasks requiring ATP in the brain:

A

Mitochondria: one neural cell body may produce up to 2000 mitochondria per day
Macromolecules (channels, enzymes, neurofilaments, etc.) are replaced daily due to loss or degradation
Neurotransmitters
Cell membrane components
Synaptic vesicles

55
Q

Glial cell activity requiring ATP:

A

i. Glycogen synthesis
ii. Myelin synthesis (remember: myelin is associated with neurons but isn’t made by neurons)
iii. Buffering of extracellular ion concentrations

A&P module 4 CNS (7 decks)

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