Cerebral Blood Flow & CNS Homeostasis (Karius) Flashcards
Describe the blood flow to the brain
The 2 internal carotid arteries & basilar artery join to form the Circle of Willis.
How does the cerebral circulation ensure survival in case theres damage to an artery
The vessels that contribute to the Circle of Willis do not mix but instead innervate separate regions of the brain. So disruption of one of the inputs produces localized areas of ischemia and not to the whole brain.
What are the innervations for cerebral circulation
- Sympathetic NS
- Parasympathetic NS
- Sensory Innervation
- Local control - Oxygen consumption
Explain Sympathetic Innervation to cerebral circulation
- Only activated when there is an increase in cardiac ouput and blood pressure.
- NT released are Norepinephrine & Neuropeptide Y (NPY) which are released from the postganglionic cell
- NT bind to alpha 1 adregnergic receptors in the brain
- Leads to constriction of blood vessels
Explain Parasympathetic innervation to Cerebral circulation
- NT relased are Acetylcholine, Vasoactive Intestinal Polypeptide (VIP) & PHM-27 and innervate larger blood vessels (which are proximal to heart)
- Causes vasodilation of blood vessels
- Physiological relevance is uncertain (in day to day life how often are they active and are they doing anything)
Explain Sensory innervation to Cerebral circulation
- Nociceptors (sensory nerve cells) release NTs: Substance P, Neurokinin A, CGRP.
- The NTs cause the blood vessels to dilate which increases blood flow to the brain.
(In presence of low CSF in brain, the brain is heavier and simple motion causes pain)
Explain the role of local control in innervating Cerebral circulation
Oxygen consumption dictates where in the brain blood goes because increased O2 consumption = increased activity of the brain. Therefore blood is directed to those areas.
What does autoregulation of cerebral blood flow mean
The blood flow in the brain is held constant at varying systemic pressures btw 60 mmHg - 140 mmHg and even higher with sympathetic innervation
How are the cerebral capillaries protected from changes in systemic blood pressure
Cerebral blow flow is strongly autoregulated. When blood pressure is high, the sympathetics in the brain will vasoconstrict the vasculature prior to reaching the capillaries so the thin capillary walls are not damaged.
This increases systemic vascular resistance, causing the heart to work harder BUT IT’S ALL ABOUT THE BRAIN
What infleunces cerebral blood flow
Intrancranial pressure – as intracranial pressure goes up, venous outflow is obstructued due to collapsed veins, leading to a reduced arterial flow.
What might increase intracranial pressure
- Hydrocephalus of any variety (increased CSF)
- Crebral Edema (swelling of brain tissue)
- Intracranial Bleeding (brain tumors)
What are the changes in systemic circulation that occur when blood flow in the brain is reduced
The brain will drive systemic blood pressure up to force blood to the brain.
BECAUSE IT’S ALL ABOUT THE BRAIN, blood pressure can be driven to very high levels in order to perfuse the brain.
What is the role of CSF
To protect the brain. Makes the brain “lighter”
Route of CSF
Lateral ventricle –> (interventricular foramen) –> Third ventricle –> (cerebral aqueduct) –> fourth ventricle –> (lateral & median apeture) –> subarachnoid space —> arachnoid villi –> Superior sagittal sinus
Where is cerebral spinal fluid produced
50-70% is made by the choroid plexus while the remaining is made by the tissue that lines the ventricles & blood vessels.
Process of making CSF
- Passive filtration of serum (removal of clotting factor proteins from plasma)
- Modification of ion composition
What does the passive filtration of serum depend on
- Hydrostatic pressure (DOMINATES)
- Oncotic pressure (the oncotic pressures cancel each other out)
Fluid moves from blood vessels into the ventricles
What substances are in equal amounts in both the plasma and CSF
Sodium and bicarbonate
What substances are in greater quantity in the CSF than plasma
Mg2+, Cl- (added)
CO2 (neuronal metabolism)
What substances are found less in the CSF than in plasma
K+
Ca2+
Protein
Glucose (needed in brain)
How does CSF enter the venous sinus
Arachnoid villi allows for bulk flow of CSF to venous sinuses. CSF flows in one direction.
What is the role of the blood brain barrier
Protect the compostition of the CSF
What are the structural adaptions that form the BBB and what are thri functions
- Tight junctions btw endothelial cells - prevents bulk flow
- Glial endfeet (podocytes) - form lipid bi-layer and increase distance of diffusion
What substances can cross the BBB
H2O - Via aquaporins
CO2 - lipid soluble
O2 - needed by neurons
Free steroid hormones
What is the major energy source for neurons
Glucose
How does Glucose enter the brain
Glut 1 (55k) - moves glucose past endothelial cells of capillary (located on capillaries)
Glut 1 (45k) - moves glucose past glial end feet of capillary to CSF
(located on astroglia)
Glut 3 - moves glucose into neurons
Mutation of what glucose transporter is not survivable
Glut 3 - moves glucose into neurons.
What happens if neurons don’t get glucose
No glucose = No ATP = No Na/K ATPase activity = Depolarization = increased excitability = Seizures = Damged neurons
Na/K/2Cl transporter
Transporter that moves all those ions from CSF to blood.
What regulates Na/K/2Cl transporter
Concentration of K+ in CSF.
Increased K+ in CSF causes a repolarization that triggers endothelial cells of the blood vessels to express endothelin 1 & 3 to remove K+ from CSF
What is p-glycoprotein (MDR-1)
Protein that shuttles substances that have gotten past the BBB back into the blood. Provided protection from toxins.
Clinical consquence of p-glycoprotein
Removes drugs that we want to get across BBB
What are the circumventricular organs
Organs that don’t have a BBB because they need access to plasma composition
- Posterior Pituitary
- Area Postrema
- OVLT
- Subfornical organ
Posterior Pituitary
Releases hormones into the blood
Area Postrema
Surface of brain where 4th ventricle opens up. Protects composition of blood by eliciting vomiting.
OVLT & Subfornical organ
Control of total body water, thirst, blood volume control
