2. Cerebral Vasculature and Brain Homeostasis Flashcards
what is the amount and flow of CSF
how is it made
Thru the ventricles and around the brain & spinal cord ==> flow is one way and reabsorbed by arachnoid villi at the end
~150 mL at any given time & not recirculated –> so make ~550 mL/day
made primarily by choroid plexus (esp in lateral & 4th ventricle) & rest by tissue that lines the ventricles
How are the 4 ventricles connected
Intraventricular Foramen –> Lateral ventricles - 3rd ventricle
Cerebral Aquaduct–> 3rd ventricle - 4th ventricle
Median Aperture –> 4th ventricle - cisterna magna
Lateral Apertures –> 4th ventricle - arachnoid space
What happens if the ….
- intraventricular foramen
- cerebral aquaduct
- median aperture
- lateral aperture
are blocked?
CSF build up in…
- lateral ventricles
- 3rd ventricle
- 4th ventricle
- 4th ventricle
and the ones prior?*?*?*?*?*
What is stage 1 of making CSF
Step 1: Passive filtration of serum (Dependent on two pressures)
- Hydrostatic pressure (BP in capillaries = tissue hydrostatic P)
- Oncotic Pressure (cancel each other out)
–> fluid moves from blood vessel into ventricle
*RMR: production of CSF is constant over wide rances of ICPs*
What is hydrostatic pressure
- In capillary = blood pressure –> Pushes fluid out. = large force on capillaries (= net Pressure bc oncotic cancel out!)
- Surrounding the capillary = Tissue hydrostatic pressure –> Pushes fluid into capillary = small force on brain/body
what is oncotic pressure
= osmotic pressure (dep. on solutes in blood)
- In capillary => “pulls” fluid into the capillary.
- Surrounding capillary =>“pulls” fluid out of the capillary
- At the choroid plexus, these two are equal and opposite.
What is step 2 of formation of CSF
Modification of ion composition:
- HCO3, Cl, and K concentrations controlled by channels on epithelial cells. •Aquaporin 1 allows H2O to cross.
Does production of CSF fluctuate with pressure?
NO! its CONSTANT!!!
= so even if a lot of CSF or increased ICP –> STILL make more & get build up
what molecules/ions in the CSF will be in similar in concentration as plasma
- Na+ (range overlaps with average concentration in plasma
- HCO3
CSF contains more ________ than plasma
Mg++ (interact w/ channels in brain)
Cl-
CO2 (brain metabolic rate makes it ==> CSF is 1st step of getting it out and into blood)
Plasma contains higher concentrations of which molecule/ions, compared to CSF?
K+ (bc metabolic rate, dont need much bc cells push it out)
Ca++ (can be toxic for cells)
Protein (low oncotic P –> no buffer for H+ ==> pH diff from plasma as well)
Glucose
How does absorption by arachnoid villi occur
endothelium of sinus & membrane on villi are fused => bulk flow of CSF (one way flow)
absorption proportional to ICP
-at ICP < 68 mm - no absorptions ==> BUILD UP
at normal pressure ~ 112 mm = normal absorption
*control of amount of CSF based on reabsorption NOT production*
What will occur if the arachnoid villi fibrose
decrease reabsorption –> increase pressure –> damage neurons!
primary role of CSF
protect brain!
brain weighs: 1400 g in air BUT w/ CSF it weighs 50 g
(bc high lipid concentration)
=bouyancy & protection
What is the blood brain barrier (BBB) and what is its fxn?
Capillaries that limit exchange bc tight jxn btn endothelial cells & Glial endfeet in contact with BVs (add lipid bilayers- restrict things coming)
Fxn = protect chemical composition of CSF, maintain electrolyte composition (esp K+ & Vm), protect from toxins
what substances can cross the BBB via passive diffusion
H2O- via AQP4 (either direction)
CO2 (very lipid soluble)
O2
free steroid hormones (highly lipophilic)
How does glucose enter the brain
Glut-1 transporters (not insulin dependent! aka work at all times)
two types: 45K for astroglia & 55K for capillaries (one to cross membrane of endothelial cell and other to cross end plate)
glucose imp for neuron fxn (=energy source) -
what transporter do neurons use to move glucose into cell
glut 3
what controls the expression of the Na/K/2Cl transporter ?
what does this transporter do?
- endothelin 1 & 3 from endothelial cells of blood vessels (BVs)
- all moves ions from CSF to blood (seems to be related to [K+] in CSF, so if too high, then all 3 ions are kicked out of cell)
=electro-neutral movement)
what is the role of P-glycoprotein
pump glycoprotein
-bind to variety of substances (move drugs that cross BBB back out)
What are the areas in the BBB that lack tight jxn btn endothelial cells?
=places where we want brain exposed to blood (circumventricular organs)
- Posterior Pituitary - aka Neurohypohysis (= modified neural tissue, release hormones in response to blood)
- Area Postrema: vomiting (chemotoxic trigger zone)
- Organum Vasculosum of the Lamina Terminalis (OVLT)- control body water/thirst/blood volume (body osmolarity)
- Subfornical Organ- control body water/thirst/blood volume (body osmolarity)
What are characterisitcs of cerebral circulation
requires 750 ml/min (14% of blood from heart/min)
- 2 internal carotid A and the basilar A join & form Circle of Willis
- little mixing of blood from diff sources
- disruption of 1 input –> localized areas of ischemia (other areas continue to get enough blood)
What is the sym innervation of the cerebral circulation
Neurotransmitters: Norepi & Neuropeptide Y (NPY)
Receptors: alpha-adrenergics
Leads to constriction when ONLY when systemic cardiac output/blood pressure increase
what is the parasym innervation of cerebral circulation
•Innervation of larger blood vessels
- NT =-Ach
- =Vasoactive intestinal polypeptide (VIP)
- =PHM-27 (derived from pre-pro-VIP (vasoactive intestinal polypeptide)
–> cause vasodilation
what is the sensory innervation of the cerebral circulation
sensory innervation in distal blood vessels
NTs = Substance P, Neurokinin A & CGRP (all cause dilation!)
-extremely sensitive to torsion/manipulation –> cause pain (headaches!)
*these neurons release NT back onto vasculature!*
What is the role of sensory innervation of cerebral circulation
-reduced CSF volume (like after lumbar puncture) –> brain = heavier –> ‘torsion’ of the blood vessels & simple motion = pain! via….
==> Activate afferent fibers –> sense torsion & manipulation –> same neuron release NT –> vasodilation and increase blood flow
How is cerebral circulation controlled?
- Local control - O2 consumption dictates blood flow –> flow to places that are active
- Autoregulated: flow is constant over wide range of systemic (mean arterial) BP
- Influenced by ICP- hydrocephalus, cerebral edema, intracranial bleeding
what happens to cerebral circulation if you have high blood pressure
high BP –> sym innervation cause vasoconstiction –> increase systemic vascular resistance but protects capillaries in the brain and BBB from damage
How is ICP related to systemic BP
as ICP increases, venous outflow is obstructed –> decrease arterial flow –> activate cardiovascular control centers in medulla –> increase systemic BP
*–> ICP increased by hydrocephalus, cerbral edema, intracranial bleeding) <–*
What is the reason flow is constant thru a wide range of mean arterial BP?
-protect BBB b/c capillaries get damaged with high pressure, this keeps things level
when is blood flow dependent on mean arterial blood pressure
low BP (<60 mm Hg)
high HP (>140 mm Hg)
how does sympathetic stimulation influence cerebral circulation
alpha-adrenergic receptors –> constrict vessels –> extend range (where flow & BP are unrelated)
==> mechanism to protect BBB
