Cerebral Vasculature and CNS Homeostasis Flashcards
How much CSF do we have at any given moment? How much CSF do we make per day?
150 mL at any moment; 550 mL made per day
What ventricles are connected through the intraventricular foramen?
Lateral ventricles to the 3rd ventricle
What ventricles are connected through the cerebral aqueduct?
3rd ventricle to the 4th ventricle
What is connected through the median aperture?
4th ventricle to the cisterna magna
What is connected through the lateral apertures?
4th ventricle to the arachnoid space
What makes most of the CSF? What is the percentage?
Choroid plexus makes 50-70% of the CSF; the rest is made by tissue that lines the ventricles and blood vessels
What is step 1 of the formation of CSF?
Passive filtration of serum, dependent on hydrostatic pressure and oncotic/osmotic pressure
What is hydrostatic pressure in the capillary?
Equivalent to blood pressure; pushes fluid out; usually large
What is hydrostatic pressure surrounding the capillary?
Also called tissue hydrostatic pressure; pushes fluid into capillary; usually small
What is osmotic pressure in the capillary?
Pulls fluid into the capillary
What is osmotic pressure surrounding the capillary?
Pulls fluid out of the capillary
Describe osmotic pressure at the choroid plexus
Equal and opposite; the 2 osmotic pressures cancel each other out
Describe hydrostatic pressure at the choroid plexus
Blood pressure in the capillary > tissue hydrostatic pressure
What is the net flow of fluid at the choroid plexus?
Fluid moves from the blood vessels into the ventricles
What is step 2 of the formation of CSF?
Modification of ion composition; HCO3, Cl, and K concentrations are controlled by channels on epithelial cells; aquaporin 1 allows H2O to cross
T/F: Production of CSF is constant over a very narrow range of intracranial pressures
False; production of CSF is constant over a wide range of intracranial pressures
What ions tend to end up in equal concentrations in both plasma and the CSF?
Na and HCO3
What ions tend to be greater in the CSF than the plasma?
Mg, Cl, CO2
What ions tend to be less in the CSF than the plasma?
K, Ca, protein, glucose
What is the arachnoid villi? What is its function?
Endothelium of sinus and the membrane on the villi have fused; functions in reabsorbing CSF after it has flowed through the ventricular system
Absorption of CSF at arachnoid villi is proportional to intracranial pressure. At pressures below 68 mm CSF, what happens? At normal pressure (around 112 mm CSF), what happens? What does increased pressure cause?
Below 68 mm CSF: no absorption
Normal: absorption
Increased Pressure: causes damage to neurons
After being reabsorbed by the arachnoid villi, what happens to the CSF?
CSF enters venous sinuses via “bulk flow”
What limits exchange in the capillaries of the brain?
Tight junctions between endothelial cells and glial endfeet that come in close contact with a blood vessel
What are some substances that can cross the BBB?
H2O (via aquaporin 4), CO2, O2, free steroid hormones (most are protein bound)
What is the major energy source of neurons? How does this cross the BBB?
Glucose, which does NOT cross the BBB readily; crosses BBB via GLUT 1
What are the 2 forms of GLUT 1 that help glucose cross the BBB and where are they found?
55k: found on capillaries
45k: found on astroglia
What do neurons actually use to bring glucose in?
GLUT 3
What controls the expression of the Na/K/2Cl transporter? What is its expression related to?
Controlled by release of endothelin 1 and 3 from endothelial cells of the blood vessels; seems to be related to [K] in CSF
What is p-glycoprotein?
Pump glycoprotein; binds to a wide variety of substances
Many drugs do cross BBB but are moved back to the blood via p-glycoprotein
What is the function of the BBB?
Protect the chemical composition of the CSF from blood-borne pathogens; maintains electrolyte composition, particularly K; also functions in maintenance of Vm and offers protection from toxins
Describe how the BBB is “handicapped” in some portions of the brain
There are 4 regions of the brain that require exposure to blood-borne substances to function; in these regions, the capillaries do NOT have the tight junctions between endothelial cells
What are circumventricular organs?
Neural tissue that is “outside” or not as well protected by the BBB as other neural tissue
What are the 4 circumventricular organs?
Posterior pituitary, area postrema, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ
What is the function of the posterior pituitary?
Releases hormones into blood
What is the function of the area postrema?
Controls vomiting
What is the function of the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ?
Involved in control of body water/thirst/blood volume control
How much blood is required in cerebral circulation per minute?
750 mL/min (14% of blood pumped from heart every minute)
What forms the Circle of Willis?
2 internal carotid arteries and the basilar artery
What happens if you disrupt one of the inputs to the Circle of Willis?
Localized ischemia; despite appearance, there is little mixing of the blood from the different sources
For sympathetic innervation of cerebral circulation, what neurotransmitters are involved? What receptors are involved? What is the function of this sympathetic innervation?
Neurotransmitters: norepinephrine and neuropeptide Y (NPY)
Receptors: alpha-adrenergics
Function: leads to constriction when systemic cardiac output/blood pressure increases
For parasympathetic innervation of cerebral circulation, what neurotransmitters are involved? What receptors are involved? What is the function of this parasympathetic innervation?
Neurotransmitters: acetylcholine, vasoactive intestinal polypeptide (VIP), and PHM-27 (derived from pre-pro-VIP)
Receptors:
Function: innervates larger blood vessels and causes vasodilation
T/F: There is sensory innervation of the distal blood vessels
True
What neurotransmitters are involved in sensory innervation of the distal blood vessels and what is their function?
Substance P (dilation), neurokinin A (dilation), and CGRP (dilation)
What are sensory fibers to the blood vessels sensitive to?
Torsion/manipulation that can lead to pain; excruciating headaches
What is the function of these sensory fibers to the blood vessels?
In the presence of low CSF, the brain is “heavier” and simple motion can cause pain because of “torsion” on the vessels; activation of these afferents will cause vasodilation and increase blood flow, returning total intracranial volume closer to normal
What dictates where in the brain blood will go?
Oxygen consumption
We use these changes in brain metabolism/blood flow to infer activity in a variety of circumstances
T/F: Cerebral blood flow is strongly autoregulated - it is held constant over a wide range of systemic (mean arterial) blood pressures
True
In the face of high blood pressure (which could damage the BBB), sympathetics in the brain will __________ the vasculature.
Vasoconstrict
Note that although this will increase the systemic vascular resistance, it protects the capillaries in the brain and the BBB from damage
What happens when intracranial pressure goes up?
Venous outflow is obstructed, leading to reduced arterial flow; this decrease in brain perfusion will activate cardiovascular control centers in the medulla and increase systemic BP
What might increase the intracranial pressure?
Hydrocephalus of any variety, cerebral edema, and intracranial bleeding
