CNS Homeostasis Flashcards
1
Q
How much blood is required by the brain per minute?
A
750 ml/min (14% of blood pumped from heart every minute)
2
Q
What happens if there is disruption of one of the inputs of Circle of Willis?
A
Localized (discrete) areas of ischemia rather than global effects – due to fact that there is little mixing of the blood from different sources in the circle of willis
3
Q
Internal Carotid As
A
- Anterior circulation
- MCA & ACA
4
Q
Basilar A
A
- Posterior circulation
- Blood from this A does not mix with ICAs
5
Q
Systemic Circulation: Sympathetic Chemical Mediators
A
- Epinephrine (Adrenal Gland via blood)
- Norepinephrine (from nerve endings)
6
Q
Systemic Circulation: Sympathetic Receptors
A
- Alpha-adrenergic (contraction, vasoconstriction)
- Beta-adrenergic (relaxation, vasodilation)
7
Q
Systemic Circulation: Sympathetic Significance
A
Critical to maintain BP
8
Q
Systemic Circulation: PNS Chemical Mediators
A
ACh
9
Q
Systemic Circulation: PNS Receptors
A
Muscarinic (relaxation, vasodilation)
10
Q
Systemic Circulation: PNS Significance
A
- Minor direct influence
- More likely to influence via indirect mechanisms
11
Q
Cerebral Circulation: Sympathetic Chemical Mediators
A
- Norepinephrine
- Neuropeptide Y (NPY)
12
Q
Cerebral Circulation: Sympathetic Receptors
A
Alpha-adrenergic (contraction, vasoconstriction)
13
Q
Cerebral Circulation: Sympathetic Significance
A
- Protection of cerebral capillaries
- Critical when systemic BP is high
14
Q
Cerebral Circulation: Sympathetic Innervation
A
Leads to vasoconstriction when systemic CO/BP increases
15
Q
Cerebral Circulation: PNS
A
Innervation of larger blood vessels in brain
16
Q
Cerebral Circulation: PNS Chemical Mediators
A
- ACh
- Vasoactive Intestinal Polypeptide (VIP)
- PHM-27 (derived from pre-pro-VIP)
17
Q
Cerebral Circulation: PNS Receptors
A
Muscarinic (ACh)
18
Q
Cerebral Circulation: PNS Significance
A
Unknown
19
Q
Cerebral Circulation: Parasympathetic Innervation
A
Causes vasodilation
20
Q
There is ___ innervation of the distal blood vessels
A
Sensory
(means there are nociceptors)
21
Q
3 main NTs that are released and act on cerebral blood vessels:
A
(1) Substance P
(2) Neurokinin A
(3) CGRP (Calcitonin-gene related peptide)
22
Q
Substance P
A
Associated with pain
23
Q
Neurokinin A
A
Associated with damage
24
Q
CGRP
A
Associated with migraines
25
Sensory fibers within cerebral circulation are extremely sensitive to ___ /____ and lead to ___
- Torsion/manipulation
- Pain
26
Cerebral sensory innervation and reduction of CSF volume
Brain is heavier and simple motion can cause pain because of the torsion of the blood vessels
27
Activation of sensory afferents in cerebral circulation causes ____ and increased ___ ___
- Vasodilation
- Blood flow
(Brain does this b/c it is trying to bring intracranial volume back to normal until can make more/new CSF)
28
Systemic Circulation: innervated by sensory fibers?
Yes
29
Systemic Circulation: sensory fibers vasoactive?
Yes - Nociceptors
30
Systemic Circulation: Sensory Innervation Chemical Mediators
Substance P
31
Cerebral Circulation: innervated by sensory fibers?
Yes
32
Cerebral Circulation: sensory fibers vasoactive?
Nociceptors - Yes
33
Cerebral Circulation: Sensory Innervation Chemical Mediators
- Substance P
- NKA
- CGRP
34
Cerebral Circulation: Sensory Innervation Receptors
Nociceptors
35
Cerebral Circulation: Sensory Innervation Effects
Sensation of pain when head moves
36
Cerebral Circulation: Sensory Innervation Significance
- Tied with migraines
- BP significant when have low CSF levels
37
Cerebral blood flow is under ___ control
Local
38
What dictates where in the brain the blood will go?
Oxygen consumption
39
Cerebral blood flow is strongly ______
Autoregulated
- it is held constant over a wide range of systemic (mean arterial) BPs
40
Location of the synapse between pre-ganglionic and post-ganglionic neurons of the sympathetic nervous system
Paravertebral ganglia (sympathetic chain)
41
Alpha-Adrenergic Receptors
- Located on smooth muscle
- Activated by SNS (when systemic BP increases beyond normal limits)
- When activated, cause increased smooth muscle contraction, vasoconstriction and reduced blood flow to the organs receiving blood from the constricted arteries
- Primary adrenergic receptor found on the cerebral vasculature
42
Nicotinic Receptors
- Located in the synapses between pre-ganglionic and post-ganglionic neurons of both the sympathetic and parasympathetic systems
43
___ pressure in the brain is maintained constant over a wide range of systemic MAPs
Perfusion
44
As systemic BP increases:
1. Sympathetic innervation of the cerebral vasculature becomes more active
2. Release more NE
3. Binds to alpha-adrenergic receptors
4. Vasoconstriction of cerebral vasculature
Effect: protects the blood brain barrier
45
With high perfusion pressure, the ___ ___ between endothelial cells of the capillaries are damaged
Tight Junctions
46
Vasoconstriction of the arterioles during high BP prevents:
Pressure from being transmitted to the capillaries, which in turn preserves the BBB and the brain
47
Systolic BP of ___ mmHg will damage the BBB temporarily
180
48
If perfusion pressure of the brain is decreased (due to increased intracranial pressure):
- Brain acts to increase BP via centers in the brainstem that detect and control BP
- Reduced blood flow triggers increase in systemic MAP even if systemic BP is normal/high
- Brain acting to preserve its own blood flow
49
What can happen if blood flow to the brain is severely compromised?
Systemic BP can go incredibly high
50
Sign of an increase in intracranial pressure (i.e intracranial hemorrhage):
Increase in systemic BP
51
Sensory innervation of the brain via nociceptors are activated by torsion (twisting, stretching) of the blood vessels and produce:
Intense Headache
52
Why is a headache common after a lumbar puncture?
Decreased CSF volume means the brain is "heavier" and can now torque with normal motion --> pressure on distal blood vessels --> activation of nociceptors on distal blood vessels in the brain --> pain/headache
53
What is the one substance that is present in higher concentrations in the CSF than the plasma?
Magnesium
54
When below BP MAP of 60 mmHg, as MABP increases Cerebral Blood Flow (CBF) will:
Increase
55
Cerebral Blood Flow held constant between what MABPs?
60 mmHg to 140 mmHg
56
___ extends the range at which MABP is held constant -- protects capillaries and blood-brain barrier from damage
Sympathetics
57
As BP increases, sympathetics in brain trigger release of ___ and binding to its receptors
NE
(results in vasoconstriction)
58
Cerebral blood flow is influenced by ___ ___
Intracranial Pressure
59
As intracranial pressure goes up, __ ___ is obstructed, leading to ____ arterial flow
- Venous outflow
- Reduced
60
Decrease in brain perfusion will activate the cardiovascular control centers in the __ and increase ___ ____
- Medulla
- Systemic BP (increases blood flow by increasing heart rate and BP)
61
3 things that can increase ICP:
- Hydrocephalus
- Cerebral edema
- Intracranial bleeding
62
Activation of the sympathetics ___ resistance and is used when systemic BP is ___
- increases
- HIGH
63
What happens when there is cerebral edema?
Decreased perfusion to the brain --> increased blood flow --> increased HR and BP
*brain doesn't care that systemic BP rises b/c only cares about brain
64
How much CSF do you have at any given moment?
150 mL
65
CSF not recirculated, so make about ____ ml /day of CSF
550
66
Intraventricular Foramen
Connects the Lateral Ventricles to the 3rd Ventricle
67
Cerebral Aqueduct
Connects the 3rd Ventricle to the 4th Ventricle
68
Median Aperture (Foramen of Magendie)
Connects the 4th Ventricle to the Cisterna Magna
69
Lateral Aperture (Foramen of Luschka)
Connects 4th Ventricle to the Subarachnoid Space
70
Where is CSF produced?
- Choroid Plexus (50-90%)
- Remaining CSF made by the tissue that lines the ventricles and blood vessels
71
Two-Step Process of CSF formation by the Choroid Plexus
- Step 1: Creation of Osmotic Gradient
- Step 2: Movement of water across membrane
72
CSF Formation in Choroid Plexus: Step 1, Creation of Osmotic Gradient
Relies on existence of transport proteins on the membrane, many of which are ATP dependent or co-dependent
73
Ions that are critical in creating the Osmotic Gradient for CSF Formation:
- Na
- K
- Cl
- HCO3
74
CSF Formation in Choroid Plexus: Step 2, Movement of Water Across the Membrane
Aquaporin-1 allows H2O to cross and follow the osmotic gradient
75
Production of CSF is constant over a wide range of ___ ____
Intracranial Pressures
(having CSF is so critical that will not stop producing it no matter what)
76
The further away CSF gets from Choroid Plexus, the more ___ it gets from the concentration of plasma
Different
77
Components that have higher concentrations in CSF than they do in Plasma ([X]CSF > [X]Plasma):
- Na
- Mg
- Cl
78
Components that have lower concentrations in CSF than they do in Plasma ([X]CSF < [X]Plasma):
- K
- Ca
- Protein
- Glucose
79
What component is in equal concentrations in both the plasma and CSF?
HCO3-
(maintains acid/base composition)
80
Why is it important that [K+] is lower in CSF than plasma?
- AP repolarization occurs when K+ leaves the cell
- Need this so APs can occur
81
CSF is absorbed by:
Arachnoid granulations/villi
82
Absorption of CSF is ___ to ICP
Proportional
*make CSF continuously but control how much is reabsorbed
83
Absoprtion of CSF when CSF pressure is below 68 mm:
No absorption
84
What is normal pressure of CSF?
112mm
85
From the arachnoid granulations, CSF enters the venous sinuses by ___ flow
Bulk
86
Role of CSF:
protect the brain
87
Capillaries in the brain have two components that limit exchange:
- Tight junctions between endothelial cells
- Glial end feet come in close contact with blood vessel
88
Glian endfeet in contact with blood vessels are nearly:
continuous, creating perivascular space
89
Substances that can cross BBB via passive diffusion
- H2O
- CO2
- O2
- Free steroid hormones (most are protein bound)
90
How can H2O cross the BBB?
Via Aquaporin-4
91
What is the major energy source for neurons?
Glucose - does not readily cross the BBB
92
How does Glucose get across the BBB?
GLUT 1 transporter
93
Is GLUT1 insulin-dependent?
No
94
Two forms of GLUT1 receptors:
1. 55K
2. 45K
95
Where are 55K GLUT1 receptors located?
Capillaries (endothelial cells)
96
Where are 45K GLUT1 receptors located?
Astroglia
97
What do neurons use to move glucose in?
GLUT3
98
Na/K/2 Cl Transporter
Moves ions from CSF into blood
99
What controls the expression of the Na/K/Cl transporter in the BBB?
Release of endothelin 1 and 3 from endothelial cells of the blood vessels
100
The expression of the Na/K/2Cl transporter seems to be related to:
The control of [K+] in the CSF
101
P-Glycoprotein
- Pump Glycoprotein
- Binds a wide variety of substances in the CSF (i.e drugs) and moves them back into the blood
102
Gene that codes for P-Glycoprotein:
MDR1 (multi-drug resistance protein 1)
103
BBB Function
- Protects the chemical composition of the CSF form blood-borne agents
- Maintains electrolyte composition --- particularly related to K+, maintenance of Vm
- Protection from toxins
104
Glymphatics
Glial-dependent waste clearance pathway in the brain
105
Glymphatics: Step 1
Water leaves the periarterial space via Aquaporin 4 (AQP4)
106
Glymphatics: Step 2
Water exiting creates flow of ISF/CSF through the parenchyma of the brain; anything dissolved in the ECF/ISF moves with it
107
Glymphatics: Step 3
Fluid moves into perivascular spaces around the venules/veins; this is also dependent on AQP4
(creates continuous flushing of fluid around the neurons)
108
What two proteins expressed by Astroglia are instrumental in moving beta-amyloid into the perivenous space and out of the brain?
- APOE
- APOJ
109
Glymphatics: Step 4
Fluid enters the cervical lymphatics
110
When does Glymphatic flow occur?
During sleep
111
There is evidence of active suppression of glymphatic flow by ___ receptors when we are awake
Adrenergic
112
Glymphatic flow is decreased by:
- Age
- Brain ischemia or TBI
113
What is the main cause of decreased glymphatic flow?
Abnormal cellular localization of AQP4 (typically located at the end feet but in this case they are found in other parts of the astroglia's membrane)
114
Circumventricular Organs
- Neural tissue that is "outside" or not as well protected by the BBB as other neural tissue
- Regions where the capillaries do not have tight junctions between endothelial cells
- Can be secretory (no BBB so can secrete hormones) or sensory (no BBB so they can sense blood composition)
115
4 Main Circumventricular Regions
(1) Posterior Pituitary
(2) Area Postrema
(3) Organum Vasculosum of Lamina Terminalis (OVLT)
(4) Subfornical Organ
116
Circumventricular Regions: Posterior Pituitary
- Also called the Neurohypophysis
- Modified neural tissue
- Release peptide hormones into blood
- Secretory
117
Circumventricular Regions: Area Postrema
- Area that elicits vomiting because it is chemosensitive
- Sensory -- detects chemicals then elicits vomiting
118
Circumventricular Regions: OVLT and Subfornical Organ
- Both are involved in control of body water/thirst/blood volume control
- Sensory
119
Circumventricular Regions: Purpose
Allow parts of brain access to plasma composition
120
Circumventricular Regions: Consequences
Exposed to toxins that rest of brain is protected from
121
Location of Cell Bodies of Post-Ganglionic Sympathetic Fibers That Innervate Cerebral Vasculature?
Superior Cervical Ganglion
