Cerebral Blood Flow And CNS Homeostasis Flashcards
How much blood is required for cerebral circulation?
750 ml/min required (14% of blood pump from heart every min)
The two internal carotids and the basilar artery join to form what?
The circle of Willis (very little mixing of blood from the different sources)
What is the impact of a block of blood flow in the circle of Willis?
Localized (discrete) areas of ischemia
Part of the brain not the entire brain which limits the amount of brain damage to occur
Describe the sympathetic innervation to the cerebral circulation
NTs: NE and neuropeptide Y (NPY)
Receptors: alpha adrenergic
Leads to vasoconstriction when systemic cardiac output/BP increases
Describe the parasympathetic innervation of the cerebral circulation
Innervation of the larger blood vessels
NTs: ACh, vasoactive intestinal polypeptide (VIP) and PHM-27 (derived from pre-pro-VIP)
Causes vasodilation
Physiological relevance uncertain
What is the third source of innervation of the cerebral circulation?
Sensory innervation of the distal blood vessels
Describe sensory innervation to the cerebral circulation
NTs released and act on the blood vessels include substance P, neurokinin A and CGRP (can be used to treat migraines)
All cause dilation
These sensory fibers render the blood vessels of the brain extremely sensitive to torsion/manipulation and leads to pain
What is the role of sensory innervation to the cerebral circulation?
In the presence of reduced CSF volume the brain is effectively heavier and simple motion can cause pain because of the torsion of the blood vessels
The activation of those afferents will also cause vasodilation and increase blood flow (returns total intracranial volume closer to normal)
Cerebral blood is under what type of control?
Under local control
Oxygen consumption dictates where in the brain the blood will go
We use these changes in brain metabolism/blood flow to infer activity in a variety of circumstances (more active neurons = more blood flow)
How is cerebral blood flow strongly autoregulated?
It is held constant over a wide range of systemic (mean arterial) blood pressures
At which mean arterial BP values will cerebral blood flow remain constant?
60-140 mmHg which is the autoregulation of the cerebral blood flow meaning it is not controlled/dictated by the mean arterial BP
What influence does sympathetic innervation have on auto regulation?
The range of autoregulation is extended beyond 140 mmHg
Purpose is to protect the capillaries in the brain from damage by the high pressure
What is the importance of autoregulation of cerebral blood flow?
In the face of high BP which could damage the BBB sympathetic in the brain will vasoconstrict the vasculature
Although this will increase the systemic vascular resistance it protects the capillaries in the brain and the BBB from damage
Cerebral blood flow is also influenced by what factor?
Intracranial pressure
As intracranial pressure goes up venous outflow is obstructed leading to reduced arterial flow
A decrease in brain perfusion (blood flow) due to increased intracranial pressure will activate what?
Cardiovascular control centers in the medulla which will increase systemic BP (sometimes drastically, over 200mmHg)
What can increase intracranial pressure?
Hydrocephalus of any variety, cerebral edema (swelling of brain tissue) and intracranial bleeding
Tumors can also increase pressure
Describe CSF
Flows through the ventricles and around the brain and SC
150mL at any given moment
Not recirculated so structures have to make 550mL/day
What is the ventricular system that CSF flows through?
Composed of four ventricles including 2 lateral ventricles, third ventricle and fourth ventricle (over medulla and under cerebellum)
Which structures connect the ventricles?
Intraventricular foramen (lateral ventricles to 3rd ventricle) Cerebral aqueduct (3rd ventricle to 4th ventricle) Median aperture (4th ventricle to cisterna magna) Lateral apertures (4th ventricle to arachnoid space)
Most of the CSF is made by what?
Specialized tissue of the choroid plexus located in the lateral ventricle
Remaining CSF is made by tissue that lines the ventricles and blood vessels
What are the two steps of formation of CSF?
- Passive filtration of serum (plasma minus protein)
2. Modification of ion composition
Explain the first step of CSF formation (filtration)
Dependent on two pressures (hydrostatic and oncotic pressures)
The oncotic pressures cancel each other
BP in the capillary > tissue hydrostatic pressure
Fluid moves from the blood vessels into the ventricles
Describe hydrostatic pressure
In the capillaries it is = to BP and pushes fluid out (large)
Surrounding the capillaries it is known as tissue hydrostatic pressure and it pushes fluid into capillaries (small)
Describe oncotic pressure
Equal to osmotic pressure
Inside the capillary it pulls fluid into the capillary
Surrounding the capillary it pulls fluid out of the capillary
At the choroid plexus these two types of oncotic pressure are equal and opposite (cancel each other out)
Describe step 2 of the formation of CSF (modification of ions)
HCO3, Cl and K concentrations controlled by channels on epithelial cells
Aquaporin 1 allows H2O to cross
Production of CSF is constant over a wide range of what?
intracranial pressures
Which ions have equal concentrations in both the plasma and CSF?
Na
HCO3* (critical to control of pH)
Which ions have higher concentrations in CSF compared to plasma?
Mg2+ (interacts with Ca) and Cl- (from choroid plexus)
CO2 (from neuronal metabolism)
Which ions have higher concentrations in plasma compared to CSF?
K (influences Vm), Ca2+ (can be toxic in high concentrations), proteins and glucose (fuel for neurons)
Describe the absorption of CSF by arachnoid villi
Endothelium of sinus and the membrane on the villi have fused
Bulk flow of CSF into venous sinus is primary
Pinocytosis is also documented
Proportional to intracranial pressure
Increased pressure causes damage to neurons
At pressures below 68mm CSF, does absorption at the arachnoid villi occur?
No
Normal pressure ~112 mm CSF
From the arachnoid villi the CSF enters the venous sinuses by what?
Bulk flow
What is the role of CSF?
Protect the brain
Allows brain to float in the CSF and protects the brain sudden movements of our head (shock absorber)
What are the two components of capillaries in the brain that limit exchange (BBB)?
Tight junctions between endothelial cells
Glial endfeet come in close contact with blood vessels and cover the capillaries (increase distance of diffusion and are lipophilic preventing passage of hydrophilic substances in the blood)
Which substances can cross the BBB via passive diffusion?
H2O via AQP-4, CO2, O2 and free steroid hormones (most are protein bound)
What is the major energy source for neurons?
Glucose which does not cross the BBB readily
Describe transport of glucose across the BBB
GLUT1 transporter located on the membranes (not insulin dependent*)
Two forms including a 55K on capillaries and a 45K on astroglia
Neurons use GLUT3 to move glucose in (also not insulin dependent)
Describe the Na/K/2Cl transporter used for regulating the BBB
Moves all those ions from the CSF to blood
Expression of transporter is controlled by the release of endothelin 1 and 3 from endothelial cells of the blood vessels
Seems to be relegated to [K+] in CSF
Many drugs cross the BBB but are moved back to the blood via what?
P-glycoprotein (pump-glycoprotein)
Aka MDR-1 (multi drag resistance protein 1)
Binds to a variety of substances (not typically of most transporters)
Moves the molecules from CSF to blood
The BBB exists to protect what?
The chemical composition of the CSF from blood borne agents
What are the functions of the BBB?
Maintain electrolyte composition (particularly related to K and maintenance of Vm)
Protection from toxins (drugs)
What are the four regions in the brain that require exposure to blood borne substances to function?
The circumventricular organs including the posterior pituitary, area postrema (elicits vomiting if chemicals in the blood), organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (both control of body water/thirst/blood volume control)
What is the consequence of some areas of the brain being in contact with the blood?
Exposed to toxins that the rest of the brain is protected from
What allows the 4 areas of the brain to have contact with the BBB?
The capillaries in these 4 regions do not have tight junctions between endothelial cells
