Cerebral Blood Flow And CNS Homeostasis Flashcards
What ion in particular alters the RMP and thus excitability of the nuerons in the brain?
Changes in the concentration of potassium
How is the CSF recirculated?
It’s not!!
How much CSF Is made per day?
550 mL
How much CSF do we have at any given point in time?
150 mL
What are the two lateral ventricles separated by?
Septum pellucidum
What is the ventricular system made of?
4 ventricles
2 lateral
3rd
4th
What connects the lateral ventricle to the 3rd?
Intraventricular foramen
What connects the 3rd ventricle to the 4th?
Cerebral aqueduct
What connects the 4th ventricle to the cisternae magna?
Median aperture
What connects the 4th ventricle to the arachnoid space?
Lateral aperture
What makes CSF?
Choroid plexus (50-70%)
Tissues lining ventricles and blood vessels (remaining %)
What are the 2 stages of CSF production?
1 - passive filtration of plasma across choroidal capillary endothelium
2 - modification of composition of choroid plexus
What drive the passive filtration of plasma across choroidal capillary endothelium?
Pressure gradients
Hydrostatic and oncotic pressures
What is the biggest factor in the getting plasma across choroidal capillary endothelium?
Hydrostatic pressure inside the capillary
Aka Blood pressure
What are the two hydrostatic pressures present in stage 1 of CSF production?
Inside cap hydrostatic pressure (BP)
Outside cap hydrostatic pressure (tissue hydrostatic press.)
What are the two oncotic pressures present in stage 1 of CSF production?
Which is greater? What do they do?
Oncotic P of tissue (pushes out)
Oncotic P of cap. (Pushes in)
Equal to each other
Cancel each other out
Is blood pressure or tissue hydrostatic pressure greater?
Blood pressure
How is the entry of HCO3, Cl, and K into the choroid plexus CSF controlled?
Via channels on apical surface of epithelial cells
How is the entry of water to choroid plexus CSF controlled?
Aquaporin 1
How does production of CSF change w/ ICP?
Constant over a wide range of ICP
CSF has similar concentration to plasma in what?
Sodium
HCO3
What is high in CSF than in Plasma?
Magnesium
CO2
Creatine
Chloride
What is the role of Mg in the CSF?
Blocker of calcium channels
Controls calcium influx into brain
Why is CO2 greater in CSF than plasma?
Greater levels of activity in brain
What is lower in the CSF than in the plasma?
Potassium
Calcium
Protein
Glucose
Why is potassium lower in CSF than plasma?
K leak channels on neurons alter RMP and change extracellular K level
Could impact Vm of neurons
Why is calcium lower in CSF than plasma?
Natural blocker of voltage gate Na channels
Could be toxic to excitable tissues in high concentrations
What are the pHs of CSF and plasma?
7.33 and 7.4
WHat is the flow of CSF?
One way path where it is reasbored by arachnoid villi at the end
What is the pathway for the flow of CSF?
Ventricle —> foramen of magendie and Luschka —> subarachnoid space
Where are arachnoid villi present?
Subarachnoid space
What are villi?
Extensions wher earachnoid membrane is fused with the endothelium of sinus
Where do the villi extend into?
Into venous sinuses
Mostly superior sagittal sinus
What is the flow of CSF across the arachnoid membrane considered to be mostly? What is also seen?
Most is build flow
Pinocytosis w/ mesothelial cells of arachnoid villi
What is the average pressure of the CSF?
112 mm
Can CSF be compressed?
No
What is the absorption of the CSF proportional to?
Intracranial pressure
At what pressure will absorption not continue?
68 mm
what is the function of the CSF?
Protection of the brain by providing it buoyancy
What is the weight of the brain without the CSF? W/ CSF?
1400 g
50 g
How is the BBB made?
Endothelial cells with tight junctions
Glial endfeet covering capillaries
What does the BBB allow for?
Capillary modification that control the diffusion out of the capillary
What does the tight control of the BBB result in?
Prevention of proteins from entering CSF
Reduced movement of many smaller molecules
What can enter the BBB via passive diffusion?
Water
Oxygen
CO2
Free steroid hormones
How does water enter the BBB?
Passive diffusion via Aquaporin4 (AQP4)
What are the 2 forms of AQP4?
Monomer responsible for water movement
Tetramer that forms distinct freeze fractures and plays role in gas transport
What do AQP4s control?
Overall water homeostasis, protective against cerebral edema
Impacts neuronal function - even indirectly
What uses mediated transport to get across BBB?
Glucose
Na
K
CL
What does glucose use to get from the blood to the CSF?
How does glucose get from blood to neurons?
Glut 1 - insulin independent
Glut 3 - insulin dependent
Where is glut 3 found?
On neuronal cell membranes
What are the 2 forms of Glut 1?
Where are they found?
Glut1 55k - on endothelial cells of capillaries
Glut1 45k- on astroglia/podocytes
What is glut5 used by?
Microglia
How do Na, k and CL cross bbb?
Where are they moving from and to?
Na/K/2Cl transporter
From CSF to blood
What controls the expression of the Na/K/2cl transporter?
Endothelial cells of blood vessels need to express
Endothelin 1 and 3
(Expression tied to astrocytes)
How are drugs transported back to the blood after tossing the BBB?
P-glycoprotein (pump)
What does P-glycoprotein bind to?
A WIDE variety of substances
What is the role of P-glycoprotein?
Limits brain exposure to drugs that are systematically delivered
Where else is P-glycoprotein located besides the brain?
Gut
What are the functions of the BBB (more specific)
Protect chemical composition of CSF from blood borne agents
Maintains Vm - by maintaining ionic composition of CSF
(Particularly potassium)
Protects brain from endogenous and exogenous poison
Prevents NTRs from escaping into general circulation
What are the circumventricular organs?
Posterior pituitary
Area postrema
Organum vasculosum of lamina terminalis
Subfornical organ
What is special about the circumventricular organs?
They do not have tight BBB
Endothelial cell’s capillaries do not have tight junctions between them, caps are fenestrated
Allows chemicals to move freely from blood to CSF in these organs.
Why is it important that the posterior pituitary be a circumventricular organ?
Modified neural tissue that needs to release hormones into the blood in response to blood driven messages
(Also Called neruohypoPhysis)
Why is it important that the area postrema be a circumventricular organ?
Where is it located?
Caudal portion of 4th ventricle
Chemotactic trigger zone that has a role in detecting irritants/poisons in blood
Initiates vomiting
Why is it important that the organum vasculosum be a circumventricular organ?
Osmoreceptor for ADH (vasopressin)
Controls body water, thirst and blood volume
Why is it important that the Subfornical organ be a circumventricular organ?
Control body water, thirst and blood volume
Along with Organum vasculosum
How much blood does the brain require a minute?
What percent of the blood from the heart is used for this?
750 ml/min
14% of blood pumped from heart every minute
What is the arterial supply for cerebral blood flow?
2 ICAs + basilar a. = circle of Willis
What makes the Basilar a.?
2 vertebral As. That unite to form basilar a.
Why is reduced blood flow to a vessel of circle of willis bad?
Very little mixing/crossing of blood in circle of willis
Disrupted blood flow can not be corrected by other vesicles
What does the interruption of blood flow in the circle of willis allow for?
Gives specific neurological signs that allow us to pinpoint damage
What is the venous drainage of cerebral blood?
Deep veins and dural sinuses to IJV
What provides innervation to cerebral vasculature?
Sympathetic fibers
Parasympathetic fibers
Sensory axons
What NTRs do the sympathetic fibers to cerebral vasculature release?
NE
Neuropeptide Y
What receptors are heavily present for cerebral vasculature and sympathetic fibers?
What will these cause?
Alpha-adrenergic receptors
Vasoconstriction
When are the sympathetic fibers to cerebral vasculature activated?
When systemic BP is increased beyond normal limits
Causing constriction and reduces BP in capillaries in brain - limiting damage to BBB due to hypertension
What will hypertension do to the BBB?
Disrupt tight junctions of BBB
What are the NTRs present in the parasympathetic innervation to cerebral blood flow?
ACh
Vasoactive intestinal polypeptide (VIP)
PHM-27 (from pre-pro-VIP)
What does parasympathetic innervation to cerebral vasculature cause?
Vasodilation
Where do we find sensory axons for cerebral blood flow?
On smaller arteries, where they are released and act back on the blood vessels
What are the sensory axons of cerebral vasculature sensitive to?
What do they release?
Causing what?
Sensitive to stretch and torsion of blood vessels
Contain substance p, neurokinin a, and calcitonin gene-related peptide (CGRP)
Vasodilation
What happens if the CSF is reduced?
Brain is heavier and simple motion can cause pain bc of the torsion of blood vessels
What will activation due to torsion of the sensory neurons cause?
Vasodilation and increased blood flow bc they are trying to return intracranial volume closer to normal
What is cerebral blood flow controlled under mostly?
Local control via O2 consumption (activity level dependent)
What happens with increased ICP?
Reduced blood flow because of compression of blood vessels
What happens with decreased ICP?
Increased torsion of blood vessels and nerve fibers due to loss of buoyancy
What can cause decreased ICP?
Lumbar puncture
how is perfusion pressure constant over a wide range of systemic mean arterial blood pressure?
Autoregulation system of MABP
What happens with the Autoregulation system when
Systemic BP is increased?
Sympathetics are more active
Release NE —> alpha a Rs —> vasoconstrict
What is the result of activating sympathetics when systemic BP is increased?
BBB is protected due to constriction of cerebral vasculature, thus preserving brain
Makes sure tight junctions are not damaged bc it wont transmit pressure from systemic system to capillaries
What happens with the Autoregulation system when
Systemic BP is decreased?
Brainstem detects and controls BP and acts to increase it
If BP is low due to hemorrhage/shock what will the brainstem do?
Reinforce actions of baroreceptors- activating presser region, activate sympathetics to cause vasoconstriction and increase BP
When the sympathetics vasoconstrict cerebral vasculature what does this cause?
For what trade off?
Causes increased systemic vascular resistance And can damage body
BUT
It protects caps in brain and the BBB from damage
Cerebrovascular is heavily influenced by?
Intracranial pressure
What will increased ICP cause in terms of cerebrovasculature?
What will this cause in medulla?
Reduced blood flow bc of compressed vessels —> reduced arterial flow
Less blood flow to brain activation cardiovascular control centers in medulla - makes systemic BP increase
What does an increase of BP indicate in terms of brain?
Increased ICP
Due to that reduced blood flow - medulla activation feedback
What can cause an increase in ICP ?
Hydrocephalus of any variety
Cerebral edema
Intracranial bleeding (from stroke, etc.)
If blood flow to the brain is compromised what will the brain do?
What is the consequence?
Will drive SYSTEMIC BP UP to force blood to brain
Systemic BP driven up VERY very high so that brain can get blood
